From the Guidelines
Cross-tapering from gabapentin to pregabalin should be done gradually, starting with a low dose of pregabalin (75mg twice daily) while maintaining the current gabapentin dose, then reducing gabapentin by 300mg every 3-4 days and increasing pregabalin by 75mg every 3-4 days, to minimize withdrawal symptoms and maintain seizure or pain control. This approach is based on the pharmacokinetic properties of both medications, including their effects on calcium channels in the nervous system 1.
When initiating the cross-taper, it is essential to consider the patient's current gabapentin dose and adjust the pregabalin dose accordingly. For example, if a patient is taking gabapentin 1800mg daily (600mg three times daily), the cross-taper might involve reducing gabapentin to 1500mg daily while increasing pregabalin to 150mg daily, then to 1200mg gabapentin while increasing to 225mg pregabalin, and so on. The entire process typically takes 2-3 weeks, depending on the starting gabapentin dose.
Some key points to consider during the cross-taper include:
- Starting with a low dose of pregabalin (75mg twice daily) to minimize side effects
- Reducing gabapentin by 300mg every 3-4 days to avoid withdrawal symptoms
- Increasing pregabalin by 75mg every 3-4 days to maintain therapeutic efficacy
- Monitoring for side effects like dizziness, drowsiness, or edema during the transition
- Adjusting the cross-taper schedule based on individual patient response and needs, under the supervision of a healthcare provider.
The cross-taper should be individualized, taking into account the patient's medical history, current medications, and potential interactions. It is crucial to prioritize the patient's safety and well-being throughout the transition process, as both gabapentin and pregabalin can produce dose-dependent side effects, such as dizziness and sedation 1.
In terms of dosing, pregabalin has linear pharmacokinetics, making it easier to titrate than gabapentin, which has nonlinear pharmacokinetics due to saturable absorption 1. The target pregabalin dose is typically 150-300mg twice daily, although this may vary depending on the patient's response and tolerability.
Ultimately, the goal of the cross-taper is to minimize withdrawal symptoms and maintain therapeutic efficacy while transitioning from gabapentin to pregabalin. By following a gradual and supervised approach, patients can safely and effectively transition between these two medications.
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 pregabentin 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 FDA drug label does not answer the question.
From the Research
Cross-Tapering Protocol
The protocol for cross-tapering Gabapentin (Neurontin) to Pregabalin (Lyrica) involves a gradual transition to minimize potential side effects and ensure a seamless switch.
- Two different transition designs have been simulated: immediate discontinuation of gabapentin therapy with initiation of pregabalin therapy, and a gradual transition involving coadministration of 50% of the gabapentin dosage and 50% of the desired pregabalin dosage for 4 days, followed by discontinuation of gabapentin and fully targeted dosages of pregabalin 2.
- The pharmacokinetic simulations show that during the transition period in both designs, predicted pregabalin-equivalent concentrations did not depart from those calculated during periods of steady-state gabapentin or pregabalin monotherapy 2.
- The transition from gabapentin to pregabalin was seamless and rapid, with predicted pregabalin-equivalent concentrations highly comparable with plasma pregabalin concentrations within 1 day of pregabalin initiation in the immediate discontinuation model and within 1 day of gabapentin cessation in the gradual discontinuation model 2.
Considerations for Cross-Tapering
When cross-tapering gabapentin to pregabalin, it is essential to consider the following:
- The dosage levels of gabapentin and pregabalin, as the transition designs were studied at three dosage levels: gabapentin 900 mg/d to pregabalin 150 mg/d, gabapentin 1800 mg/d to pregabalin 300 mg/d, and gabapentin 3600 mg/d to pregabalin 600 mg/d 2.
- The potential for combined use of gabapentin and pregabalin in pain control, as they have been noted to have a synergistic effect without concern for clinically significant pharmacokinetic interactions 3.
- The pharmacology and mechanism of action of pregabalin, which involves binding to the alpha2-delta subunit of voltage-gated calcium channels, reducing the synaptic release of several neurotransmitters and accounting for its actions in vivo to reduce neuronal excitability and seizures 4.