What are the effects of combining gabapentin (Neurontin) and pregabalin (Lyrica)?

From the Guidelines

Combining gabapentin and pregabalin is not recommended due to the potential for increased side effects without significant additional benefit, as they work through similar mechanisms and can lead to enhanced drowsiness, dizziness, confusion, and respiratory depression. The use of combination therapies for neuropathic pain has been explored in several studies, including a 2010 review of recommendations for the pharmacological management of neuropathic pain, which discussed the potential benefits and limitations of combining different medications 1. However, the specific combination of gabapentin and pregabalin was not directly addressed in this study.

Key Considerations

• Both gabapentin and pregabalin are gabapentinoids that bind to calcium channels in the nervous system to reduce pain signals, suggesting that their combined use may not provide significant additional benefit.
• The potential for increased side effects, such as drowsiness, dizziness, confusion, and respiratory depression, is a concern when using these medications together.
• In rare cases where combination therapy is considered, it should only be done under close medical supervision with careful dose adjustments, typically using lower doses of each medication than would be used individually.

Alternative Approaches

• Optimizing the dose of a single agent or switching completely from one to the other may be a better approach for patients finding inadequate relief with one of these medications.
• Consulting with a healthcare provider is essential before making any changes to a medication regimen, especially with centrally-acting drugs that require careful titration and monitoring. Some studies have examined the combination of other medications for neuropathic pain, such as gabapentin and extended-release morphine, or pregabalin and extended-release oxycodone, but the evidence for combining gabapentin and pregabalin specifically is limited 1.

From the FDA Drug Label

The pharmacokinetic interactions of pregabalin and gabapentin were investigated in 12 healthy subjects following concomitant single-dose administration of 100-mg pregabalin and 300-mg gabapentin and in 18 healthy subjects following concomitant multiple-dose administration of 200-mg pregabalin every 8 hours and 400-mg gabapentin every 8 hours Gabapentin pharmacokinetics following single- and multiple-dose administration were unaltered by pregabalin coadministration. The extent of pregabalin absorption was unaffected by gabapentin coadministration, although there was a small reduction in rate of absorption

The combination of gabapentin and pregabalin does not have a significant effect on the pharmacokinetics of either drug. However, additive effects on cognitive and gross motor functioning may occur when these drugs are co-administered.

• Key points: + No significant pharmacokinetic interactions + Additive effects on cognitive and gross motor functioning possible + No clinically important effects on respiration seen [2] [3]

From the Research

Effects of Combining Gabapentin and Pregabalin

• The combination of gabapentin and pregabalin has been used in both clinical and research situations, with a synergistic effect in pain control without concern for clinically significant pharmacokinetic interactions 4.
• However, the use of both medications concomitantly can lead to adverse effects such as drowsiness, dizziness, fatigue, and ataxia, as reported in a case study 5.
• The pharmacokinetics and pharmacodynamics of pregabalin and gabapentin differ, with pregabalin having a more rapid absorption and higher bioavailability than gabapentin 6.
• A comparative study of gabapentin and pregabalin in a palliative care population found that both medications had similar pain scores and reduction in pain, but those receiving gabapentin were more likely to experience harms such as somnolence, ataxia, nausea, tremor, and nystagmus 7.
• A systematic review and meta-analysis found that pregabalin demonstrated superior and faster efficacy in alleviating neuropathic pain than gabapentin, with improved patient-reported outcomes, lower opioid consumption, and fewer adverse events 8.

Pharmacokinetic Considerations

• Gabapentin is absorbed slowly after oral administration, with maximum plasma concentrations attained within 3-4 hours, while pregabalin is absorbed more rapidly, with maximum plasma concentrations attained within 1 hour 6.
• The absolute bioavailability of gabapentin drops from 60% to 33% as the dosage increases from 900 to 3600 mg/day, while the absolute bioavailability of pregabalin remains at > or = 90% irrespective of the dosage 6.

Clinical Implications

• The combination of gabapentin and pregabalin should be used with caution, taking into account the potential for adverse effects and the need for careful monitoring of patients 4, 5.
• The choice between gabapentin and pregabalin should be based on individual patient needs and responses, with consideration of the pharmacokinetic and pharmacodynamic differences between the two medications 6, 7, 8.