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Pregabalin in Palliative Care

  • Jennifer Pruskowski PharmD
  • Robert Arnold MD

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Background      Pregabalin (Lyrica®) is a second generation antiepileptic drug that was developed after gabapentin (See Fast Fact #049). This Fast Fact will review pregabalin and its role in palliative care. A comparison between pregabalin and gabapentin is also available (See Fast Fact #289).

Pharmacology     Pregabalin binds to the alpha-2 (α-2δ) subunit of voltage-gated calcium channels in the CNS, subsequently inhibiting the release of excitatory neurotransmitters.  Its oral bioavailability is ≥90% and can be taken with or without food. Peak plasma concentrations occur within 1.5 hours.  Pregabalin does not bind to plasma proteins, undergoes negligible metabolism, and does not affect the major CYP450 enzymes in humans.  It is unlikely to have significant drug interactions (1,2).

Dosing      Starting dose for pregabalin is 150 mg/day in two to three divided doses, and may be increased to 300 mg/day within 1 week. Maximum daily dose is 450 mg/day and 600 mg/day (in divided doses) for fibromyalgia and other neuropathic pain disorders, respectively.

Dosing in Renal Impairment and Failure       Pregabalin must be adjusted for patients with a CrCl <60 mL/min, as it is approximately 90% renally eliminated (2).

Adverse Drug Reactions and Cautions    Dizziness is the most commonly reported side effect, followed by somnolence which is the most frequent reason for discontinuation. Other side effects are dose-dependent and reversible — dry mouth, angioedema, peripheral edema, blurred vision, weight gain, and difficulty with concentration/attention (3).

Research Data     Pregabalin is FDA indicated for several non-cancer pain syndromes including: diabetic peripheral neuropathy, post-herpetic neuralgia, fibromyalgia, and neuropathic pain associated with spinal cord injury, as well as an adjunctive therapy for adult patients with partial onset seizures.  The number needed to treat for a 50% reduction in diabetic neuropathic pain is 4 when pregabalin is dosed at 600 mg/day (4).  There is limited information for its use in cancer-related neuropathic pain (5).  In a double-blind, placebo-controlled, randomized trial in patients with neuropathic cancer pain, pregabalin was compared to gabapentin, amitriptyline and placebo; VAS scores were significantly lower in the pregabalin group, and there were clinically significant morphine sparing effects of pregabalin (6).  One randomized, controlled trial suggests low-dose pregabalin (25-50 mg/day) as an effective adjuvant for cancer related bone pain (7).

Cost     Pregabalin comes in a 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg oral capsules, and 20 mg/mL oral solution. It is not available as a generic formulation.  Pregabalin is approximately eight to ten times more costly than amitriptyline, and three times more costly than venlafaxine ER and gabapentin.

Summary     Pregabalin is a relatively expensive medication that may have a role in management of neuropathic pain associated with in cancer, several non-cancer syndromes, and as an adjuvant to opioids for painful bone metastases. 

References:

  1. Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010 Oct;49(10):661-9.
  2. Pregabalin (Lyrica®) [package insert]. New York, NY: Pfizer Parke-Davis; 2004.
  3. Eisenberg E, River Y, Shifrin A, et al. Antiepileptic drugs in the treatment of neuropathic pain. Drugs 2007; 67 (9): 1265-89.
  4. Bril V, England J, Franklin GM, Backonja M, Cohen J, Del Toro D, Feldman E, Iverson DJ, Perkins B, Russell JW, Zochodne D; American Academy of Neurology; American Association of Neuromuscular and Electrodiagnostic Medicine; American Academy of Physical Medicine and Rehabilitation. Evidence-based guideline: Treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011 May 17;76(20):1758-65
  5. Bennett MI, Laird B, van Litsenburg C, Nimour M. Pregabalin for the management of neuropathic pain in adults with cancer: a systematic review of the literature. Pain Med. 2013 Nov;14(11):1681-8.
  6. Mishra S, Bhatnagar S, Goyal GN, Rana SP, Upadhya SP. A comparative efficacy of amitriptyline, gabapentin, and pregabalin in neuropathic cancer pain: a prospective randomized double-blind placebo-controlled study. Am J Hosp Palliat Care. 2012 May;29(3):177-82.
  7. Nishihara M, Arai YC, Yamamoto Y, Nishida K, Arakawa M, Ushida T, Ikeuchi M. Combinations of low-dose antidepressants and low-dose pregabalin as useful adjuvants to opioids for intractable, painful bone metastases. Pain Physician. 2013 Sep-Oct;16(5):E547-52.

Authors’ Affiliations: University of Pittsburgh Medical Center, Pittsburgh, PA.

Conflict of Interest: The authors have disclosed no relevant conflicts of interest.

Version History: First published March 2015.