Switching between gabapentin and pregabalin for neuropathic pain

Switching between gabapentin and pregabalin for neuropathic pain

If treatment is not effective or tolerated, NICE guidance for neuropathic pain in adults recommends switching to an alternative treatment (1)

• may include switching between the gabapentinoids: gabapentin and pregabalin (1)

Neuropathic pain states are typically managed by super-adding anticonvulsant drugs onto simple drug regimens

• drugs most commonly used are gabapentin (GBP) or pregabalin (PGB)
• pregabalin and GBP are both analogs of gamma-aminobutyric acid, a substance known to modulate calcium channel subunits
• both GBP and PGB may therefore possibly act by decreasing neurotransmitter release associated with central sensitization in CS and neuropathic pain (2)
• study evidence showed PGB and GBP were both significantly efficacious (2)
  • GBP was superior with fewer and less severe adverse events

Gabapentin to pregabalin dose equivalence calculation

• using the 6:1 ratio an equivalent dose of gapapentinoid can be determined using a step-wise approach (1)
• determine total dose (in mg) taken by an individual in a 24-hour period
• divide total daily dose (in mg) of gabapentin by 6 to give total daily dose of pregabalin (in mg)
• divide total daily pregabalin dose (in mg) by the desired frequency of administration
• pregabalin is usually given twice or three times a day - decide frequency on a case-by-case basis taking individual preference and clinical characteristics into account

Notes:

• pregabalin is available as 25mg, 50mg, 75mg, 100mg, 150mg, 200mg, 225mg and 300mg tablets and capsules
• round the dose up or down to the nearest practical dose
• a decision to round up or down, or to use asymmetrical dosing (e.g. 150mg in the morning and 175mg at night), should be based on individual preference and clinical characteristics

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
• determine total dose (in mg) taken by an individual in a 24-hour period
• multiply total daily dose (in mg) of pregabalin by 6 to give total daily dose of gabapentin (in mg)
• divide total daily gabapentin dose (in mg) by three

Notes:

• gabapentin is available as 100mg, 300mg and 400mg capsules and 600mg and 800mg tablets
• round the dose up or down to the nearest practical dose
• a decision to round up or down, or to use asymmetrical dosing (e.g. 300mg in the morning, 300mg at lunchtime and 400mg at night), should be based on individual preference and clinical characteristics

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

• are three different switching strategies described by the manufacturer
• 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 (1)

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 (1)
• after two to four days discontinue the initial medication and continue with the replacement drug at full equivalent dosage (1)

Taper and switch

• this method follows the manufacturer's recommendation
• slow withdrawal is important for individuals with epilepsy to maintain seizure control (1)
  • 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 (1)
• for the next scheduled dose, prescribe an initiation dosage of the replacement medication and titrate upwards as directed in the gabapentin or pregabalin SmPC (1)

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

Dose equivalences

• guidance from the Best Practice Advocacy Centre New Zealand modifies the 6:1 ratio (1)
  • 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 (1)

Reference:

• NHS Specialist Pharmacy Service (January 2023). Switching between gabapentin and pregabalin for neuropathic pain
• Robertson K, Marshman LAG, Plummer D, Downs E. Effect of Gabapentin vs Pregabalin on Pain Intensity in Adults With Chronic Sciatica: A Randomized Clinical Trial. JAMA Neurol. 2019 Jan 1;76(1):28-34. doi: 10.1001/jamaneurol.2018.3077. Erratum in: JAMA Neurol. 2019 Jan 1;76(1):117.