Pharmacology Update: Pregabalin Capsules (Lyrica™)

By William T. Elliott, MD, FACP, Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco, Associate Editor, Internal Medicine Alert, and James Chan, PhD, PharmD, Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA, Associate Editor, Internal Medicine Alert.

Pregabalin has been approved for the management of neuropathic pain. It is the second drug to be approved for the treatment of painful diabetic neuropathy (after duloxetine) and the first drug to be approved for both diabetic neuropathy and postherpetic neuralgia. Pregabalin is pharmacologically similar to gabapentin. It will be marketed by Pfizer as LyricaTM.

Indications

Pregabalin is indicated for the management of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia.

Dosage

The initial dose is 150 mg daily (in 2 to 3 divided daily doses) and may be increased after 3 to 7 days to 300 mg and to 600 mg after 7 days. The dose should be reduced in patients with renal impairment.

Pregabalin is expected to be available as 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg capsules.

Potential Advantages

Pregabalin is the first drug to be approved for both diabetic neuropathy and postherpetic neuralgia. In randomized, placebo-controlled studies, pregabalin provided significant improvement in pain relief, reduction in sleep interference, and various other secondary measures.1-5

Potential Disadvantages

The most common side effects include dizziness, somnolence, dry mouth, peripheral edema, blurred vision, weight gain, and difficulty concentrating. Peripheral edema is the third most common dose-related adverse event usually beginning within 2-4 weeks after drug initiation.4,5 This event does not appear to be associated with worsening of underlying cardiovascular condition. Pregabalin requires dosing 2 to 3 times daily.

Comments

Pregabalin is a 3-substituted analog of gamma-amino butyric acid similar to gabapentin. It is believed be similar to gabapentin in pharmacological action.1,2 Randomized, placebo-controlled studies in both postherpetic neuralgia and peripheral diabetic neuropathy were of very similar design. Primary end points were pain reduction based on an 11-point scale. Secondary end points included daily sleep interference score and various other measures that may differ among studies. These included quality-of-life surveys, patient and clinical global impression of change. Effective doses of pregabalin were 150 mg to 600 mg/d. Patients were excluded if they had previously not responded to doses of gabapentin > 1200 mg/d. The percentage of patients with = 50% reduction in mean daily pain scores ranged from 26-50% for pregabalin 150 to 600 mg, compared to 10-20% for placebo. Significant improvements were also observed in weekly mean sleep interference scores, patient and clinician global impression and various quality-of-life surveys. Significant improvement was observed at week one. The most common side effects were dizziness (10-39% vs 2-15% for placebo), somnolence (5-27% vs 3-7%), and peripheral edema (3-19% vs 1-5%).1,2 Side effects were dose dependent. The median onset of dizziness or somnolence was 2 to 3 days.5 Discontinuation of therapy also appeared to be dose dependent, 32% (600 mg/d), 16% (300 mg), 11% (150 mg), 10% (placebo).1 There are currently no published comparative trials with gabapentin, lidocaine patch, duloxetine, or tricyclic antidepressants (eg, nortriptyline). Studies with similar design have reported a similar magnitude of pain reduction with gabapentin relative to placebo.6,7 Pregabalin is not yet available pending its classification as a controlled medication. Cost is also not available.

Clinical Implications

Neuropathic pain can be a debilitating form of pain. In the United States, about 1 million people may be affected by postherpetic neuralgia and another 3 million affected by painful diabetic neuropathy.1,2 Pregabalin is the first drug to be approved for both diabetic peripheral neuropathy and postherpetic neuralgia. Due to the lack of comparative studies it’s not known if it offers any clear clinical advantages over other drugs including its predecessor, gabapentin, which is available generically.

References

1. Frampton JE, Scott LJ. Drugs. 2004;64(24):2813-2820.

2. Frampton JE, Foster RH. Drugs. 2005;65(1):111-118.

3. Sabatowski R, et al. Pain. 2004;109:26-35.

4. Lesser H, et al. Neurology. 2004;63:2104-2110.

5. Dworkin RH, et al. Neurology. 2003;60:1274-1283.

6. Rowbotham M et al. JAMA. 1998;280:1837-1842.

7. Backonja M et al. JAMA. 1998;280:1831-1836.