Cappuzzo rash severity, and inﬂammation and fever are thought to all have an effect on PHN severity.3 PHN pain is often severe, unrelenting, and exhausting. As a result, PHN can dramati- cally affect a patient’s quality of life and functional status. Patients may develop insomnia, weight loss, chronic fatigue, and an inability to perform daily activities. It is estimated that more than 50% of patients with PHN have sleep disturbances, and about 25% report a decrease in socialization. Eventually a patient with PHN may lose the ability for self-care, leading to depression and social isolation.1,2,7,8 Successful management of PHN can be complicated and challenging, especially with the fact that there is no deﬁnitive treatment algorithm speciﬁcally for patients with PHN. In recent years, there have been a number of published guidelines proposed for the treatment of neuropathic pain in general.5,9–12 These recommendations are essentially based on evidence of efﬁcacy from randomized controlled trials (RCTs) of pharmacologic therapies; there is a lack of clinical trials directly comparing efﬁcacy and safety of one pharmacotherapy versus another.12,13 These guidelines uniformly recommend tricyclic antidepressants (TCAs), opioids, and anticonvulsants as ﬁrst-line therapeutic options for treating neuropathic pain. First or second-line recommendations include topical treat- ments (eg, topical lidocaine), depending on the source. Both gabapentin and pregabalin (PGB) are oral anticonvulsants approved for the management of PHN. They are both recommended as ﬁrst-line therapeutic choices for neuropathic pain based on several RCTs.5,9–12 Although there have been no head-to-head RCTs between these 2 agents in patients with PHN, both have signiﬁcantly reduced pain (p 0.01) and improved sleep (p 0.01).7,15–18 This review will focus speciﬁcally on PGB, the newest agent to gain approval for PHN. A general overview of the drug will be given, followed by a review of clinical trial efﬁcacy and adverse effects data in PHN patients, concluding with a discussion of PGB’s place in therapy in treating PHN. Pregabalin overview: pharmacology and pharmacokinetics PGB was ﬁrst approved in the European Union by the European Agency for the Evaluation of Medicinal Products for the treat- ment of peripheral neuropathic pain in July 2004. PGB received conditional approval by the US Food and Drug Administration for the treatment of diabetic peripheral neuropathy (DPN) and PHN in December 2004 and was granted ﬁnal approval after controlled substance scheduling by the US Drug Enforcement Agency in August 2005.19 PGB is a schedule V controlled sub- stance based on a study with 15 recreational sedative/hypnotic 18 drug users who rated the “desirability” of a single dose of PGB 450 mg as similar to a single dose of diazepam 30 mg.19–21 Indeed, euphoria was reported in 4% of PGB-treated patients versus 1% of placebo-treated patients in over 5500 patients in controlled clinical trials, and withdrawal symptoms suggestive of physical dependence were reported upon abrupt discontinu- ation of PGB in some studies.20 The exact mechanism of action of PGB is unclear but is thought to be similar to that of gabapentin. PGB is a structural analogue of GABA, but it is inactive at GABA-A or -B receptors, it is not converted into GABA or a GABA antagonist, and it does not affect GABA uptake.7,21,22 PGB is an alpha2-delta ligand. PGB may alter the release of several neurotransmitters, by selectively binding to the alpha2-delta auxiliary protein subunit of voltage-gated calcium channels. By tightly binding to alpha2-delta protein, PGB reduces the inﬂux of calcium, thereby reducing the release of neurotrans- mitters, including glutamate, norepinephrine, and substance P. These mechanisms are thought to result in the anticonvulsant, anxiolytic, and analgesic properties exhibited by PGB. PGB was created in an attempt to develop a compound that would retain the biologic activity of gabapentin while improving its pharmacokinetic proﬁle. PGB is well absorbed following oral administration with an oral bioavailabil- ity of 90%. The bioavailability of gabapentin actually decreases from 60% to 27% with increasing doses due to saturable absorption (900 mg/day versus 4800 mg/day, respectively).20,21,23 Unlike gabapentin, PGB exhibits linear pharmacokinetics. Elimination of PGB is virtually propor- tional to creatinine clearance (CrCl). Dosage adjustments for renal dysfunction are provided (Table 1). Ninety-eight percent of a dose of PGB is excreted unchanged in the urine, and the drug undergoes negligible metabolism with no anticipated CYP 450 enzyme drug interactions. PGB pharmacokinetics do not appear to be affected by race or gender and have not been studied in pediatric patients.20,21,24 Renal clearance of PGB appears to decrease with age, consistent with age-related changes in renal function. Hence, older adults often require renal adjustment of PGB dosing.20 PGB is effectively cleared by hemodialysis; 50%–60% is removed from the circula- tion following a 4-hour hemodialysis session. Therefore, a supplemental dose should be given immediately following every 4-hour hemodialysis treatment (Table 1).20,21,24 Literature review: pregabalin for PHN The efﬁcacy of PGB for management of PHN has been dem- onstrated in 3 double-blind, placebo-controlled, multicenter Clinical Interventions in Aging 2009:4