Prescribing gabapentin and pregabalin: upcoming subsidy changes

Start with an analgesia plan

Whenever medicines are prescribed for pain, it is best practice to create an analgesia plan with the patient, which can be discussed verbally and written down. A plan should provide the patient with clear instructions on how to use their medicines appropriately, including the dose and frequency, when or if they can increase the dose, common adverse effects and how to reduce the dose and stop medicines as their pain improves. Agree on a review schedule, e.g. seeing the patient again within two to four weeks of initiating a medicine or changing a dose, in order to assess the development of adverse effects and how well their pain is controlled.

An example of a pain management template is available from: www.guild.org.au.

Initiating and escalating doses

Gabapentin requires an initial slower titration than pregabalin to minimise the incidence of dose-related adverse effects, such as sedation and dizziness.² A dosing protocol is given in Table 1. However, for either medicine clinicians may prefer to use a much slower titration to a reach a dose that is maximally effective, while minimising adverse effects. Patients who are more susceptible to adverse effects, such as frail elderly people, may be started on lower doses than shown in Table 1, and titrated more gradually.¹² For example, initiate gabapentin 100 mg, once daily at night, increasing to 100 mg, twice daily, then 100 mg, three times daily. Some patients may require one week at each dose before increasing to the next.

Reduced doses are required in patients with renal impairment

Pregabalin and gabapentin are not metabolised to a significant extent and are excreted in the urine unchanged. They do not affect the metabolism of other medicines, such as oral contraceptives or anticonvulsants.¹³ Reduced doses are required in patients with an eGFR ≤ 80 mL/minute/1.73m² for gabapentin or ≤ 60 mL/minute/1.73m² for pregabalin; refer to the NZF for specific dosing recommendations for patients with renal function below these thresholds: gabapentin – www.nzf.org.nz/nzf_2629 pregabalin – www.nzf.org.nz/nzf_2631

Table 1:Dosing comparisons of gabapentin and pregabalin.^{3, 13, 14}

Table 2: Common adverse effects in patients taking pregabalin or gabapentin.^{15, 22, 23}

Changing or combining medicines for neuropathic pain

Increasing the dose or switching to another first-line medicine for neuropathic pain may be appropriate for patients who experience a partial response but feel that the pain relief is still inadequate.⁶ If a first-line medicine has not produced sufficient benefit, withdraw the medicine and initiate a different first-line medicine, e.g. a tricyclic antidepressant if gabapentin or pregabalin has been insufficient, or vice versa. Despite the fact that pregabalin and gabapentin have similar mechanisms of action, clinical experience suggests that patients who do not respond to one of these medicines may still derive benefit from the other.²⁷ If patients have not found any of the first-line medicines sufficiently beneficial, consider combination treatment with two first-line medicines (see below).

Gradual dose reduction over seven days is recommended when withdrawing patients from gabapentin or pregabalin as abrupt discontinuation can cause insomnia, nausea, sweating and anxiety; slower withdrawal may be necessary in some patients.⁶ There is little evidence to help guide clinicians regarding appropriate strategies to switch patients between these medicines.²⁸ In some clinical trials, patients have abruptly stopped one medicine and started the other the following day without reporting adverse effects.²⁸ Alternatively, a slower process of switching could be carried out, such as halving the dose of the original medicine, and introducing the second at half the intended dose for the first few days, then stopping the original medicine and continuing treatment with the second at the full dose.²⁸

A combination of first-line medicines may be trialled: Combining medicines with different mechanisms of action may provide patients with better analgesia than higher doses of a single medicine.²⁹ For example in one study, nortriptyline 50 mg, daily, with gabapentin 2000 mg, daily in divided doses, provided better pain relief than nortriptyline 60 mg, daily or gabapentin 2250 mg, daily alone. Although the combination of gabapentin with pregabalin is sometimes used in practice, there is little evidence to support this and subsidy is not available for both medicines concurrently.^{9, 30}

Re-consider the diagnosis of neuropathic pain or consider whether an underlying condition is worsening if patients have trialled multiple first-line medicines without benefit.

Add opioids with caution

In some cases, first-line medicines will not be sufficient in patients with severe neuropathic pain and they will also require an opioid, e.g. tramadol or morphine. Gabapentin or pregabalin can be continued in patients prescribed opioids, however, caution is required as the combination of these medicines can increase the risk of potentially fatal adverse effects, such as respiratory and CNS depression. The risk of accidental overdose is also increased and the ability to perform tasks such as driving or operating machinery may be affected.²⁴

Regularly consider the need for continued use of medicines

Although in many cases neuropathic pain is ongoing due to an underlying degenerative or non-treatable condition, in some cases medicines for neuropathic pain will be prescribed for a condition where improvement is possible or expected, e.g. post-herpetic neuralgia or post-surgery. Regular review of the ongoing need for analgesia is recommended. Expectations for duration of treatment and a plan for withdrawal of medicines are best set when treatment is first initiated.