Reasons for switching

If treatment is not effective or tolerated, NICE guidance for neuropathic pain in adults recommends switching to an alternative treatment. This may include switching between the gabapentinoids: gabapentin and pregabalin.

Considerations before switching

Consider the following points before switching and consult local policy if available.

Evidence base

There is no consensus or national guidance on how to switch. The evidence base on switching between gabapentinoids is limited because:

• only a small number of studies have reported on switching
• most data collected relates to a switch from gabapentin to pregabalin
• studies describe different dose equivalences
• studies describe different switching strategies

Licensing

Pregabalin is licensed for peripheral and central neuropathic pain whereas gabapentin is licensed for peripheral neuropathic pain only.

Use of gabapentin for central neuropathic pain is therefore off-label. However, gabapentin is recommended by NICE as a first-line treatment option for adults with all types of neuropathic pain (except trigeminal neuralgia).

Interactions

There are no clinically relevant pharmacokinetic interactions between gabapentin and pregabalin. Additive pharmacodynamic effects may occur if gabapentin and pregabalin are taken concurrently during a switch as they have a similar mode of action.

Renal function

Gabapentin and pregabalin both require dose adjustment in individuals with reduced renal function.

Consult the summary of product characteristics (SmPC) for gabapentin and pregabalin for further information before determining an equivalent dose and switching strategy.

High doses

Pregabalin is relatively more dangerous than gabapentin in high doses. Blood concentrations of pregabalin increase in proportion to an increasing dose. Whereas, gabapentin blood concentrations do not increase proportionally with an increasing dose.

Safety alerts have been issued for both agents to highlight risk of respiratory depression. Consider adjustments in dose or dosing regimen for individuals at higher risk of respiratory depression.

Dose equivalences

The original substitution study used dose equivalences of the author’s own creation. Later studies used a 6:1 ratio of total daily dose of gabapentin to pregabalin. This ratio has become established in local-level NHS guidance.

More recently, guidance from the Best Practice Advocacy Centre New Zealand modifies the 6:1 ratio. This is to account for how the two drugs behave differently with increasing doses. If using this guidance to determine a dose equivalence, be aware it includes doses of gabapentin greater than the maximum UK-licence.

Gabapentin to pregabalin dose equivalence calculation

Using the 6:1 ratio an equivalent dose of gapapentinoid can be determined using a step-wise approach

Worked example

A 35-year-old man takes 700mg of gabapentin three times a day for neuropathic pain. Due to lack of efficacy, you wish to switch to twice daily pregabalin. Use the step-wise approach, to calculate an appropriate dose of pregabalin:

1. 700mg x 3 times a day = 2100mg gabapentin daily
2. 2100mg ÷ 6 = 350mg pregabalin daily
3. 350mg ÷ 2 doses = 175mg pregabalin to be given twice a day
4. Suitable strengths are available so this dose can be facilitated without rounding up or down. However, consider individual preference and clinical characteristics before prescribing a final dose.

Pregabalin to gabapentin dose equivalence calculation

Using the 6:1 ratio an equivalent dose of gapapentinoid can be determined using a step-wise approach

Worked example

A 42-year-old woman takes 200mg of pregabalin twice a day for neuropathic pain. Due to lack of efficacy, you wish to switch to gabapentin. Use the step-wise approach, to calculate an appropriate dose of gabapentin:

1. 200mg x 2 times a day = 400mg pregabalin daily
2. 400mg x 6 = 2400mg gabapentin daily
3. 2400mg ÷ 3 doses = 800mg gabapentin to be given three times a day
4. Suitable strengths are available so this dose can be facilitated without rounding up or down. However, consider individual preference and clinical characteristics before prescribing a final dose.

Switching strategies

There are three different switching strategies described by the manufacturer or presented in the literature. These are listed below (in no order of preference). Decide the best option on a case-by-case basis taking individual preference and clinical characteristics into account.

Direct switch

This method is described in the literature and has been widely used in local-level NHS guidance.

How to conduct a direct switch

• Prescribe what will be the final dose of the initial medication.
• For the next scheduled dose, substitute with an equivalent dosage of the replacement medication.

Cross-tapering

This method is described in the literature.

How to conduct cross-tapering

• Prescribe half the dosage of the initial medication along with half an equivalent dosage of the replacement medication for two to four days.
• After two to four days discontinue the initial medication and continue with the replacement drug at full equivalent dosage.

Taper and switch

This method follows the manufacturer’s recommendation. Slow withdrawal is important for individuals with epilepsy to maintain seizure control. However, the importance of slow withdrawal in individuals with neuropathic pain is unknown.

How to conduct a taper and switch

• Prescribe a reducing dosage of the initial medication so that over at least a week the dosage reaches zero.
• For the next scheduled dose, prescribe an initiation dosage of the replacement medication and titrate upwards as directed in the gabapentin or pregabalin SmPC

Monitoring after the switch

Monitor clinical efficacy and adjust dose in response to therapeutic effect, tolerability, and adverse reactions.

Consider referring the individual to NHS patient information on using gabapentin or pregabalin.

Bibliography

Full referencing is available on request.

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