Pregabalin Extended Release

PREGABALIN EXTENDED RELEASE- pregabalin tablet, film coated, extended release
Alvogen Inc.

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1 INDICATIONS AND USAGE

Pregabalin extended-release tablets are indicated for the management of:

• Neuropathic pain associated with diabetic peripheral neuropathy
• Postherpetic neuralgia

Efficacy of pregabalin extended-release tablets has not been established for the management of fibromyalgia or as adjunctive therapy for adult patients with partial onset seizures.

2 DOSAGE AND ADMINISTRATION

2.1 Important Dosage and Administration Instructions

Pregabalin extended-release tablets should be administered once daily after an evening meal.

Pregabalin extended-release tablets should be swallowed whole and should not be split, crushed, or chewed.

When discontinuing pregabalin extended-release tablets, taper gradually over a minimum of 1 week.

Instruct patients that if they miss taking their dose of pregabalin extended-release tablets after an evening meal, then they should take their usual dose of pregabalin extended-release tablets prior to bedtime following a snack. If they miss taking the dose of pregabalin extended-release tablets prior to bedtime, then they should take their usual dose of pregabalin extended-release tablets following a morning meal. If they miss taking the dose of pregabalin extended-release tablets following the morning meal, then they should take their usual dose of pregabalin extended-release tablets at the usual time that evening following an evening meal [see Patient Counseling Information (17)].

2.2 Neuropathic Pain Associated with Diabetic Peripheral Neuropathy

Begin dosing at 165 mg once daily and increase to 330 mg once daily within 1 week based on individual patient response and tolerability. The maximum recommended dose of pregabalin extended-release tablets is 330 mg once daily.

Although pregabalin was studied at 600 mg/day, there was no evidence that this dose conferred additional significant benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions with pregabalin, treatment with doses above 330 mg/day is not recommended for pregabalin extended-release tablets.

2.3 Postherpetic Neuralgia

Begin dosing at 165 mg once daily and increase to 330 mg once daily within 1 week based on individual patient response and tolerability.

Patients who do not experience sufficient pain relief following 2 to 4 weeks of treatment with 330 mg once daily and who are able to tolerate pregabalin extended-release tablets, may be treated with up to 660 mg once daily. In view of the dose-dependent adverse reactions and the higher rate of treatment discontinuation due to adverse reactions, dosing above 330 mg/day should be reserved only for those patients who have on-going pain and are tolerating 330 mg daily. The maximum recommended dose of pregabalin extended-release tablets is 660 mg once daily.

2.4 Conversion from Pregabalin Capsules or Oral Solution to Pregabalin Extended-Release Tablets

When switching from pregabalin to pregabalin extended-release tablets on the day of the switch, instruct patients to take their morning dose of pregabalin as prescribed and initiate pregabalin extended-release tablets therapy after an evening meal.

Table 1. Conversion from Pregabalin Capsules or Oral Solution to Pregabalin Extended-Release Tablets

Pregabalin Total Daily Dose(dosed 2 or 3 times daily)	Pregabalin Extended-Release Tablets Dose(dosed once a day)
* 247.5 mg = 3 × 82.5 mg tablets taken once a day. † 495 mg = 3 × 165 mg tablets taken once a day. ‡ 660 mg = 2 × 330 mg tablets taken once a day.
75 mg/daily	82.5 mg/day
150 mg/daily	165 mg/day
225 mg/daily	247.5 mg/day *
300 mg/daily	330 mg/day
450 mg/daily	495 mg/day †
600 mg/daily	660 mg/day ‡

2.5 Patients with Renal Impairment

Use of pregabalin extended-release tablets is not recommended for patients with creatinine clearance (CLcr) less than 30 mL/min or who are undergoing hemodialysis. Those patients should receive pregabalin.

In view of dose-dependent adverse reactions and because pregabalin is eliminated primarily by renal excretion, adjust the dose in patients with reduced renal function. Base the dose adjustment in patients with renal impairment on CLcr, as indicated in Table 2. To use the dosing tables, an estimate of the patient’s CLcr in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the Cockcroft and Gault equation:

Next, refer to the Dosage and Administration section to determine the recommended total daily dose based on indication, for a patient with normal renal function (CLcr greater than or equal to 60 mL/min). Then refer to Table 2 to determine the corresponding renal adjusted dose.

(For example: A patient initiating pregabalin extended-release tablets therapy for postherpetic neuralgia with normal renal function [CLcr greater than or equal to 60 mL/min], receives a single daily dose of 165 mg/day pregabalin. Therefore, a renal impaired patient with a CLcr of 50 mL/min would receive a single daily dose of 82.5 mg.)

Table 2. Pregabalin Extended-Release Tablets Dosage Adjustment Based on Renal Function

Creatinine Clearance (CLcr)(mL/min)	Total Pregabalin Extended-Release Tablets Daily Dose(mg/day)				Dose Regimen
* 495 mg = 3 × 165 mg tablets taken once a day. † 660 mg = 2 × 330 mg tablets taken once a day. ‡ 247.5 mg = 3 × 82.5 mg tablets taken once a day.
greater than or equal to 60	165	330	495*	660†	Once a day
30–60	82.5	165	247.5‡	330	Once a day
less than 30/hemodialysis	Dose with Pregabalin