How Gabapentin Differs From Pregabalin

SEPTEMBER 21, 2015
Converting from gabapentin to pregabalin
For clinicians who wish to convert patients from gabapentin to pregabalin, there are a few studies that reviewed such a conversion.
 
One cohort study reviewed the utility of switching patients with neuropathic pain due to peripheral neuropathy from gabapentin to pregabalin.10 The study followed patients who were switched from gabapentin to pregabalin and then compared them to those who stayed on gabapentin. The authors also stratified the pregabalin group further into those who responded well or poorly to gabapentin, with gabapentin stopped after the nighttime dose and pregabalin started the following morning.
 
Dosages were switched using the following algorithm:
  • Gabapentin ≤900 mg/day → pregabalin 150mg/day
  • Gabapentin 901 mg/day to 1500 mg/day → pregabalin 225 mg/day
  • Gabapentin 1501 mg/day 2100 mg/day → pregabalin 300 mg/day
  • Gabapentin 2101 mg/day 2700 mg/day → pregabalin 450 mg/day
  • Gabapentin >2700 mg/day → pregabalin 600 mg/day
This rapid change was generally well tolerated by patients.
 
The authors found that those who responded well to gabapentin and those who did not showed additional benefit with decreased pain when they were switched to pregabalin. Patients taking pregabalin also had improved pain control compared with those who remained on gabapentin.
 
Switching to pregabalin resulted in improved pain relief and also fewer adverse events. This was particularly true for patients who previously responded to gabapentin.
 
Patients who experienced adverse events with gabapentin were more likely to also experience adverse events with pregabalin. These patients were also more likely to discontinue use of pregabalin than those who responded well to both gabapentin and pregabalin.10
 
Another small trial compared the degree of pain relief with gabapentin to pregabalin in patients with postherpetic neuralgia in order to more closely determine equivalent dosing between the 2 medications.11
 
Patients were switched from gabapentin to pregabalin using one-sixth the dose of gabapentin with unchanged dosage frequency. After switching medications, patients reported similar pain relief and side effects, with the exception of an increased incidence of peripheral edema in the pregabalin group.
 
The authors concluded that the analgesic effect of pregabalin was about 6 times that of gabapentin.11
 
Other studies have looked at methods for converting gabapentin to pregabalin. One such trial used population pharmacokinetic models to examine 2 possible scenarios for converting gabapentin to pregabalin, using a ratio of 6:1 gabapentin to pregabalin.9
 
The first scenario involved discontinuing gabapentin and immediately starting pregabalin at the next scheduled dosing period. The other option included a gradual transition from gabapentin to pregabalin.
 
In this second scenario, the gabapentin dose was decreased by 50%, and 50% of the desired pregabalin dose was given concurrently for 4 days. After this time, gabapentin was discontinued and pregabalin was increased to full desired dose.
 
The model looked at transitioning patients from gabapentin to pregabalin at various doses, including:
  • Gabapentin 900 mg/day → pregabalin 150 mg/day
  • Gabapentin 1800 mg/day → pregabalin 300 mg/day
  • Gabapentin 3600 mg/day → pregabalin 600 mg/day
Both scenarios were quick and seamless, so the authors concluded that either technique could be an effective method to switch patients between the medications.9
 
Final thoughts
Though pregabalin and gabapentin have somewhat similar pharmacokinetic and pharmacodynamic profiles, there are clearly significant differences. Overall, pregabalin has more predictable pharmacokinetics, and it also shows a stronger binding affinity to its target receptor, increased potency, and a steeper dose-response curve in neuropathic pain that does not plateau over recommended dosing levels.
 
A few studies have found that pregabalin has fewer side effects and may be more efficacious for neuropathic pain than gabapentin. Several studies reviewing conversion of gabapentin to pregabalin predict that a rough ratio for conversion is about 6:1 gabapentin to pregabalin. In addition, a direct switch from gabapentin to pregabalin seems to be well tolerated, making the conversion simple.
 
Clinicians should note that pregabalin has various pharmacokinetic and pharmacodynamic advantages over gabapentin, and a conversion between the 2 medications is often well tolerated.
 
This article was written collaboratively with Daralyn A Morgenson BS, PharmD. Dr. Morgenson received her BS in psychology from the University of Nebraska-Lincoln and her PharmD from the University of Nebraska Medical Center College of Pharmacy. She is currently completing a PGY1 pharmacy residency at the Stratton VA Medical Center, with a focus on ambulatory care.

This article is the sole work of the authors and stated opinions/assertions do not reflect the opinion of employers, employee affiliates, and/or pharmaceutical companies listed. 

References
  1. Toth C. Substitution of gabapentin therapy with pregabalin therapy in neuropathic pain due to peripheral neuropathy. Pain Med. 2010;11(3):456-65.
  2. Blommel ML, Blommel AL. Pregabalin: an antiepileptic agent useful for neuropathic pain. Am J Health Syst Pharm. 2007;64(14):1475-82.
  3. Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinetics. 2010;49(10):661-9.
  4. Neurontin [Package insert]. New York, NY: Park-Davis, Division of Pfizer; December 2013.
  5. Lyrica [Package insert]. New York, NY: Park-Davis, Division of Pfizer; December 2013.
  6. Horizant [Package insert]. Santa Clara, CA: Xenoport Inc; July 2015.
  7. Gralise [Package insert]. Newark, CA; May 2014.
  8. Moore RA, Wiffen PJ, Derry S, Toelle T, Rice AS. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2014;4:CD007938.
  9. Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010;49(10):661-9.
  10. Toth C. Substitution of gabapentin therapy with pregabalin therapy in neuropathic pain due to peripheral neuropathy. Pain Med. 2010;11(3):456-65.
  11. Ifuku M, Iseki M, Hidaka I, Morita Y, Komatus S, Inada E. Replacement of gabapentin with pregabalin in postherpetic neuralgia therapy. Pain Med. 2011;12(7):1112-6.


Jeffrey Fudin, PharmD, DAIPM, FCCP, FASHP
Jeffrey Fudin, PharmD, DAIPM, FCCP, FASHP
Dr. Jeff Fudin graduated from Albany College of Pharmacy & Health Sciences with a BS and PharmD. He is a Diplomate to the Academy of Integrative Pain Management, a Fellow to ACCP, ASHP, & FSMB, a member of several other professional organizations. He is CEO of Remitigate (remitigate.com), an opioid safety software development LLC. Dr. Fudin is a section editor for Pain Medicine & Co_Editor-A-Large for Practical Pain Management. He practices as a clinical pharmacy specialist (WOC) and director of PGY-2 pharmacy pain residency programs at the Stratton Veterans Administration Medical Center in Albany, New York and has academic affiliations with Western New England University and Albany Colleges of Pharmacy.
SHARE THIS
57