Download QA408_3_Pregabalin_gabapentin_March2015

Medicines Q&As
Q&A 408.3
How do you switch between pregabalin and gabapentin for
neuropathic pain, and vice versa?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Date prepared: March 2015
Background
Both gabapentin and pregabalin were originally developed as antiepileptic drugs. Gabapentin, along
with the originator brand of pregabalin (Lyrica) are also licensed for neuropathic pain. In March 2015,
NHS England released guidance on prescribing pregabalin for neuropathic pain: “Pregabalin should
only be prescribed for the treatment of neuropathic pain under the brand name Lyrica® (unless there
are clinical contra-indications or other special clinical needs e.g. patient allergic to an excipient,
branded product unavailable etc which apply to Lyrica®, when you should not prescribe Lyrica® or
pregabalin).”1,2,3,4
The mechanism of action is similar for pregabalin and gabapentin. Both drugs bind to the α 2δ subunit
of voltage-gated calcium channels1,2. Gabapentin has nonlinear pharmacokinetics, meaning careful
titration of dose is required, whereas pregabalin possesses linear pharmacokinetics, which mean
dosing regimes are more straightforward5.
Pregabalin is recommended as one of the first-line treatment options for neuropathic pain (alongside
amitriptyline, duloxetine and gabapentin), by the National Institute for Health and Clinical Excellence 6.
This recommendation was seen as controversial at the time of publication of the guideline, as
gabapentin was in common use prior to this time7.
Answer
There have been no clinically relevant pharmacokinetic interactions found between pregabalin and
gabapentin8, although pregabalin displaces gabapentin from receptors9.
The manufacturer of both pregabalin and gabapentin advises that if they are to be discontinued, or
the dose reduced or substituted with an alternative medication, the dose should be tapered gradually
over a minimum of a week1,2. However, this withdrawal is to minimise the risk of increased seizure
frequency where they are being used for patients with seizure disorders 10. The clinical importance of a
slow withdrawal in patients with neuropathic pain remains unknown.
Literature Search
There is very limited evidence in the medical literature with regards to managing a switch between the
two agents.
A conference abstract of a small study included 26 patients who were directly switched from
gabapentin to pregabalin. The focus of the study was looking at unlicensed doses of pregabalin and
gabapentin for the treatment of pain models outside of the pregabalin license. Patients were switched
directly to pregabalin after stopping gabapentin with no dose tapering or wash out period. Most
patients were switched to 150mg twice daily of pregabalin (above the recommended licensed starting
dose in the UK). Unfortunately, there was no reported information on tolerability of this switching
regime11.
An open label study substituted gabapentin with pregabalin in patients with neuropathic pain due to
peripheral neuropathy. The author describes an overnight switch from gabapentin to pregabalin,
based on a conversion table which is described in the paper as “of the author’s creation” (table 1). No
serious adverse effects appeared to have been caused by the switch. Patients who had not
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
responded to gabapentin therapy appeared to have a higher likelihood of adverse effects such as
sedation and dizziness, although these did not lead to treatment discontinuation after one week 12.
Daily Dose of
gabapentin pre-switch
(mg/day)
0-900
901-1500
Daily dose of pregabalin per day
post switch (mg/day)
Dosing schedule of pregabalin
150
225
75mg twice daily
75mg in the morning and 150mg in
the evening*
1501-2100
300
150mg twice daily
2101-2700
450
150mg in the morning and 300mg
in the evening
2700 or higher
600
300mg twice daily
Table 1: Dose conversion of gabapentin to pregabalin used in the Toth study.
*the table in the published study actually reads 75mg in the morning and 225mg in the evening. This error has
been corrected in the above table.
Yilmaz et al conducted a cross-over study design in which patients with neuropathic pain due to spinal
cord injury were randomised into either the pregabalin or gabapentin group. Patients were titrated up
to the highest tolerated dose up to 1800mg per day for gabapentin and 300mg per day for pregabalin
for a total of 8 weeks. After a washout period of 2 weeks, they were switched to the other medication.
Tolerability of this switching regime was not reported.13
A small (n=32) study of patients with post-herpetic neuralgia saw patients switched from gabapentin
to pregabalin at one sixth of the gabapentin dose. No serious side effects occurred, and no significant
difference was found before and after substitution in the number of patients with somnolence and
dizziness. A significant (p<0.05) increase in the number of patients with peripheral oedema was found
after the switch14.
Manufacturer’s Information
Pfizer, the manufacturer of both Lyrica® (pregabalin) and Neurontin® (gabapentin), advise that in the
absence of clinical studies, licensed dosage information for both gabapentin and pregabalin should be
consulted. They are unable to make any recommendations regarding initiating or switching 15.
An in-house pharmacokinetic simulation suggests that a regime of halving the original gabapentin
dose, and introducing half the intended dose of pregabalin on day 0, then stopping gabapentin and
doubling the pregabalin dose on day 4 leads to fairly stable drug levels of pregabalin equivalents.
However, the efficacy and safety of this switching regime has not been established, and use in this
way would fall out with the licenses of the products15.
Another unpublished pharmacokinetic simulation study was conducted in 14 healthy patients. Four
different switching scenarios were simulated. Based on these simulations, comparable therapeutic
effect would be expected using daily doses of gabapentin 3600 mg/day and pregabalin 450 mg/day. 16
Summary
In the absence of more detailed data, recommendations cannot be made about initiating or switching
to gabapentin following pregabalin treatment or vice versa. The individual SPCs suggest that both
agents should be discontinued over the course of a week, although whether this is relevant for
patients with neuropathic pain remains unclear.
Any decisions made will need to be based on a clinical judgement, in partnership with the patient.
Pain clinics or individual Clinical Commissioning Groups may have developed local switching
guidance which should be consulted where possible.
Limitations
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
This Medicines Q&A does not consider the potential for differences in efficacy of pregabalin and
gabapentin but merely considers how to manage a switch.
Quality Assurance
Prepared by
Vincent Cassidy, Regional Drug & Therapeutics Centre
(Amended by Hayley Johnson, Regional Drug & Therapeutics Centre)
Date Prepared
3rd November 2014
(Amended 17th March 2015)
Checked by
Hayley Johnson, Regional Drug & Therapeutics Centre
(Amendments checked by: Sue Dickinson, Regional Drug & Therapeutics Centre)
Date of check
20th January 2015
Amendments checked on: 17th March 2015
Search strategy
Embase
1. EMBASE; PREGABALIN/ [Limit to: Human and Publication Year 2012-2014]; 2594 results.
2. EMBASE; GABAPENTIN/ [Limit to: Human and Publication Year 2012-2014]; 3924 results.
3. EMBASE; NEUROPATHIC PAIN/ [Limit to: Human and Publication Year 2012-2014]; 4523 results.
4. EMBASE; 1 AND 2 AND 3 [Limit to: Human and Publication Year 2012-2014]; 463 results.
Medline
5. MEDLINE; Pregabalin.ti,ab; 1806 results.
6. MEDLINE; gabapentin.ti,ab [Limit to: Publication Year 2012-2014]; 860 results.
7. MEDLINE; NEURALGIA/ [Limit to: Publication Year 2012-2014]; 1887 results.
8. MEDLINE; 5 AND 6 AND 7 [Limit to: Publication Year 2012-2014]; 34 results.
eMC
NICE
Micromedex
Manufacturer’s medical information department
References
1
Summary of Product Characteristics- Neurontin 100 mg Hard Capsules (gabapentin). Pfizer Ltd.
Accessed via http://www.medicines.org.uk/emc/medicine/17095 on 21/10/2014. [date of revision of
the text 26/06/13]
2 Summary of Product Characteristics- Lyrica Capsules (pregabalin). Pfizer Ltd. Accessed via
http://www.medicines.org.uk/emc/medicine/14651 on 21/10/2014. [date of revision of the text
06/08/2014]
3 Summary of Product Characteristics- Alzain Capsules (pregabalin). Dr Reddy’s Laboratories Ltd.
Accessed via http://www.medicines.org.uk/emc/medicine/30054 on 17/03/2015. [date of revision of
the text: 10/02/2015]
4 NHS England Pregabalin Guidance, March 2015. Accessed via http://www.england.nhs.uk/wpcontent/uploads/2015/03/pregabalin-guidance.pdf
5 Dworkin r, O’Connor A, Audette J et al. Recommendations for the pharmacological management of
neuropathic pain: An overview and literature update. Mayo Clinical Proceedings 2010; 85(3): S3-S14
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
6
National Institute of Health and Clinical Excellence. NICE CG173. Neuropathic Pain: the
pharmacological management of neuropathic pain in adults in non-specialist settings. 2013. Accessed
via http://www.nice.org.uk/guidance/cg173 on 05/11/2014
7 Why  pregabalin ? DTB 2010;48:61 doi:10.1136/dtb.2010.04.0029. Accessed via
http://dtb.bmj.com/content/48/6/61.extract on 05/11/2012
8 Baxter K, Preston C (Eds), Stockley’s Drug Interactions. [online] London: Pharmaceutical Press.
Accessed via www.medicinescomplete.com on 05/11/2012.
9 Bazire S. Pregabalin. In: Psychotropic Drug Directory 2009, page 356
10 Gajraj N. Pregabalin: its pharmacology and use in pain management. Anasethesia and alangesia
2007; 105(6) 1805-1815
11 Allen S. Pregabalin- is it any better than gabapentin? Presented at the IASP’s 11 th World Congres
on Pain: Sydney, Australia 2005, cited in: Personal Communication with Medical Information- Pfizer
Ltd 27/11/2012
12 Toth C. Substitution of gabapentin therapy with pregabalin therapy in neuropathic pain due to
peripheral neuropathy. Pain Medicine 2010; 11: 456-465
13 Yilmaz B, Yasar E, Koroglu Omac O et al. Gabapentin vs pregabalin for the treatment of
neuropathic pain in patients with spinal cord injury: a cross over study. European Journal of Pain
Supplements. 2011; 5(1): 239
14 Ifuku M, Iseki M, Hidaka I et al. Replacement of gabapentin with pregabalin in postherpetic
neuralgia therapy. Pain medicine 2011; 12: 1112-1116.
15 Personal Communication with Medical Information- Pfizer Ltd 27/11/2012
16 Personal Communication with Medical Information- Pfizer Ltd 30/12/2014
Available through NICE Evidence Search at www.evidence.nhs.uk
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