New Drug Reviews
Pregabalin (Lyrica) for the Management of Pain Associated with Diabetic Neuropathy
Am Fam Physician. 2006 Dec 15;74(12):2093-2094.
Pregabalin (Lyrica) is indicated for the management of pain associated with diabetic neuropathy and postherpetic neuralgia. It also is indicated as adjunctive therapy in adults with partial onset seizures.1 Although the mechanism of action is not fully known, pregabalin seems to decrease the presynaptic release of neurotransmitters (e.g., substance P, glutamate) that are involved with pain sensation and transmission. It does not affect the underlying neuropathy or slow the progression.2
|Name||Starting dosage||Dose form||Approximate monthly cost*|
50 mg three times daily
25-mg, 50-mg, 75-mg, 100-mg, 150-mg, 200-mg, 225-mg, and 300-mg capsules
$180 for 50-mg and 100-mg capsules
*—Average wholesale cost, based on Red Book, Montvale, N.J.: Medical Economics Data, 2006.
Results from clinical trials with pregabalin have not identified serious safety issues, although euphoria and signs of physical dependence may occur. One in 25 patients reported euphoria.1 Abrupt discontinuation of pregabalin may lead to insomnia, headache, nausea, and diarrhea, and patients therefore should be gradually tapered off over a minimum of one week.1 Pregabalin is a schedule V controlled substance. Studies assessing long-term safety have not been conducted. Pregabalin is eliminated primarily by renal excretion and requires dose adjustment in patients with renal impairment.1 It is U.S. Food and Drug Administration pregnancy category C.
Approximately one in 11 patients (9 percent) will discontinue use of pregabalin because of side effects. Dizziness and somnolence are the most common side effects causing discontinuation. If dizziness or somnolence occur, the symptoms will begin shortly after initiation of treatment and in patients receiving higher doses. Dizziness occurs in almost one in three patients (29 percent), and somnolence occurs in about one in five patients (22 percent); however, only one in 25 patients (4 percent) will discontinue treatment because of these.1 In patients receiving pregabalin, dry mouth, edema, weight gain, blurred vision, and difficulty concentrating occur at twice the rate seen in those receiving placebo.1
The manufacturer of pregabalin conducted four studies comparing pregabalin with placebo in patients with painful diabetic neuropathy.2–5 Three of these studies were conducted in patients with diabetic peripheral neuropathy and one study was conducted in patients with either diabetic peripheral neuropathy or postherpetic neuralgia.2–5 Pregabalin 300 mg per day decreased mean pain scores by 2.5 points from an average of 6.5 points on a visual analog pain rating scale (ranging from 0 to 10).4 In contrast, the scores among patients receiving placebo decreased only by an average of 0.8 points. A change of 2 or more points in pain intensity is considered to be clinically noticeable by patients with diabetic neuropathy.6
A 300-mg daily dosage of pregabalin appeared to be optimal for most patients. A dosage of 150 mg per day was, on average, no more effective than placebo,2,5 and a dosage of 600 mg per day provided no greater relief than a dosage of 300 mg per day.1 In clinical trials, three-times-daily dosing resulted in a noticeable pain reduction as early as one week after initiation of pregabalin.2,4 Twice-daily dosing demonstrated a slower onset of pain reduction (i.e., two weeks).3
No studies have compared pregabalin with tricyclic antidepressants, gabapentin (Neurontin), or duloxetine (Cymbalta) for the management of painful diabetic peripheral neuropathy. The long-term effectiveness of pregabalin in the treatment of diabetic neuropathy has not been established; the longest clinical trial was only 12 weeks in duration.3
Both the initial dosage of pregabalin (50 mg three times daily) and the typically effective dosage (100 mg three times daily) will cost the patient approximately $180 per month. This cost is higher than some other options for treatment, including Cymbalta ($109) and generic amitriptyline ($1 to $19), but it is lower than the cost of Neurontin ($269) and generic gabapentin ($195 to $282).
The recommended initial dosage for pregabalin in the management of neuropathic pain associated with diabetic peripheral neuropathy is 50 mg three times daily (150 mg per day); this may be increased to 100 mg three times daily (300 mg per day) after one week based on patient response.1 Patients with renal dysfunction should be dosed following guidelines in the product labeling.1 Pregabalin can be taken with or without food.
Pregabalin is safe and effective for the management of neuropathic pain associated with diabetic peripheral neuropathy. Drawbacks include the cost and the lack of studies demonstrating equivalence or superiority to other treatments. However, pregabalin’s ease of dosing titration, minimal drug interactions, and favorable side effect profile make it appealing for those who cannot tolerate less-expensive alternatives. Until research establishes a relative benefit of pregabalin, it is better suited as a second-line therapy or as an alternative treatment option if less-expensive medications fail.
1. Lyrica (pregabalin) [Product information]. New York, N.Y.: Pfizer, Inc., 2006. Accessed July 31,2006, at: http://www.pfizer.com/pfizer/download/uspi_lyrica.pdf.
2. Lesser H, Sharma U, LaMoreaux L, Poole RM. Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial. Neurology. 2004;63:2104–10.
3. Freynhagen R, Strojek K, Griesing T, Whalen E, Balkenohl M. Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomized, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens. Pain. 2005;115:254–63.
4. Rosenstock J, Tuchman M, LaMoreaux L, Sharma U. Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial. Pain. 2004;110:628–38.
5. Richter RW, Portenoy R, Sharma U, LaMoreaux L, Bockbrader H, Knapp LE. Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial. J Pain. 2005;6:253–60.
6. Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity on an 11-point numerical pain rating scale. Pain. 2001;94:149–58.
STEPS new drug reviews cover Safety, Tolerability, Effectiveness, Price, and Simplicity. Each independent review is provided by authors who have no financial association with the drug manufacturer.
The series coordinator for AFP is Allen F. Shaughnessy, Pharm.D., Tufts University Family Medicine Residency Program, Malden, Mass.
Copyright © 2006 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact email@example.com for copyright questions and/or permission requests.
Want to use this article elsewhere? Get Permissions