Pregabalin (LYRICA): OK for Certain Seizures, but Not Pain

The airwaves are filled with ads promoting remedies for different types of pain. One such recent television ad promoted pregabalin (LYRICA) for treatment of pain due to fibromyalgia, a poorly understood chronic illness affecting more than 5 million U.S. adults.[1] Symptoms of the disorder include muscle and joint pain, stiffness, fatigue, and difficulty sleeping.[2] The ad opens with a young mother talking about her experience with fibromyalgia:[3]

I was living with pain all over. The intense ache made it hard to do the things that I wanted. My doctor diagnosed it as fibromyalgia, thought to be the result of overactive nerves that cause chronic widespread pain. LYRICA is believed to calm these nerves. I learned LYRICA can provide significant relief from fibromyalgia pain, so now I can do more of the things I enjoy.

The ad continues with the woman walking through a carnival with her daughter, appearing healthy and happy, while the narrator rattles off a list of potentially serious side effects.

So is pregabalin a good option for managing pain due to fibromyalgia and other conditions? The assessment of Public Citizen’s Health Research Group: No, it certainly is not.

Multiple FDA-approved uses

The Food and Drug Administration (FDA) initially approved pregabalin in December 2004 to treat two painful conditions. The first was neuropathic pain (pain resulting from nerve damage) in patients with diabetes.[4] This chronic disorder occurs in about 15 percent of diabetic patients.[5] Many of these patients experience numbness or tingling before the sensations progress to pain. The pain typically feels like a severe sharp, burning or stabbing sensation, most commonly in the hands and feet.

Pregabalin also was approved in 2004 to treat patients who experience neuropathic pain after having a shingles skin infection, which is caused by the chicken pox virus.[6] The painful condition develops most commonly in people who contract shingles after age 60.[7] The condition occurs in the area of the shingles rash, but it lasts for several months and sometimes for years after the rash heals.[8] The pain from this condition also typically feels like a severe aching, burning or stabbing sensation.[9]

In 2005, the FDA approved pregabalin for treatment of partial-onset seizures, the disease for which the drug was originally developed.[10] Partial-onset seizures — also called focal seizures — are caused by abnormal electrical activity in a limited area of the brain.[11] Symptoms may include:[12]

• Abnormal muscle contractions, such as abnormal head movements.
• Staring spells, sometimes with repetitive movements, such as picking at clothes or lip smacking.
• Side-to-side eye movement.
• Abnormal sensations, such as numbness, tingling or a sensation like ants crawling on the skin.
• Hallucinations.
• Blackout spells.
• Changes in vision.
• Sensations of déjà vu (feeling like current events have been experienced before).

In 2007, pregabalin was approved to treat fibromyalgia, the indication for which the drug has been most heavily promoted in direct-to-consumer ads.[13]

Most recently, in 2012, the drug was approved for treatment of neuropathic pain related to spinal cord injury.[14]

Pregabalin for pain: Do not use

Despite the FDA’s decision to approve this drug to treat four types of pain disorders, we recommend that it not be used for these purposes because the benefits have not been shown to outweigh the drug’s potentially serious side effects.

The primary FDA medical officer responsible for reviewing the applications for approval of pregabalin for diabetic and shingles-related neuropathic pain concluded that the drug should not be approved for these uses. The medical reviewer’s concerns about risks focused on significant increases in vision abnormalities in patients using pregabalin, as well as increased rates of accidental injuries and swelling. Among pregabalin users, there was a fourfold increase in blurred vision and a nearly sevenfold increase in double vision, compared with those taking a placebo pill. Accidental injuries occurred nine times more frequently in pregabalin users.

Despite the FDA medical reviewer’s concerns, his supervisors overruled him, and the drug was approved for these two indications.

Since pregabalin’s initial approval, additional safety problems have come to light. For example, cases of worsening chronic heart failure were reported in older patients using the drug for neuropathic pain.[16],[17] This adverse effect may be due to fluid retention and swelling, which are side effects of pregabalin.

Abnormal heart rhythms also have been reported in patients treated with the drug.[18] The pregabalin label warns that it should be used with caution in patients with heart failure.[19]

There is also evidence that the drug causes sexual dysfunction in both men and women. Some men taking pregabalin have experienced erectile dysfunction and decreased libido. In women, there have been cases of inability to have an orgasm as well as decreased libido.[20]

Pregabalin presents the same risks to patients with fibromyalgia and those with neuropathic pain related to spinal cord injury.

If you are taking pregabalin for any of the above pain conditions, take this article to your doctor and discuss other treatment options. Be aware that pregabalin must not be stopped suddenly, because seizures may occur. When discontinuing the drug, the dose should be gradually tapered over a week.

Pregabalin for seizures: Limited use

In contrast to the drug’s indications for neuropathic pain, the benefits of pregabalin for treating partial-onset seizures outweigh the risks for some patients. Many patients who experience partial-onset seizures respond inadequately to other available seizure drugs. Up to 12 percent of adults facing this condition may become seizure-free by adding pregabalin to other seizure drugs.[21],[22],[23],[24],[25]

In 2008, the FDA required that all manufacturers of seizure drugs, including pregabalin, add a warning to the drugs’ labeling about an increased risk of suicidal thoughts and behaviors. The agency also required that patients prescribed these drugs be provided an FDA-approved Medication Guide describing this risk.[26]

References

[1] Centers for Disease Control and Prevention. Fibromyalgia. http://www.cdc.gov/arthritis/basics/fibromyalgia.htm. Accessed October 2, 2014.

[2] Food and Drug Administration. Approval letter to C.P. Pharmaceuticals International C.V. for NDA 21-446/S-010. June 21, 2007. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2007/021446s010ltr.pdf. Accessed October 3, 2014.

[3] Anson P. Are Lyrica commercials realistic? National/Pain Report.com. February 19, 2014. http://americannewsreport.com/nationalpainreport/lyrica-commercials-realistic-8823055.html. Accessed October 2, 2014.

[4] Food and Drug Administration. Approval letter to Pfizer Global Research and Development for NDA 21-446. December 30, 2004. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2004/21446ltr.pdf. Accessed October 3, 2014.

[5] Rosenstock J, Tuchman M, LaMoreaux L, Sharma M. Rosenstock J. Pregabalin for the treatment of painful diabetic peripheral neuropathy. Pain. 2004;110:628-638.

[6] Food and Drug Administration. Approval letter to Pfizer Global Research and Development for NDA 21-723. December 30, 2004. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2004/21723ltr.pdf. Accessed October 3, 2014.

[7] Medline Plus. Postherpetic neuralgia. http://www.nlm.nih.gov/medlineplus/ency/article/007423.htm. Accessed October 3, 2014.

[8] Ibid.

[9] Ibid.

[10] Food and Drug Administration. Approval letter to C.P. Pharmaceuticals International C.V. for NDA 21-724. June 10, 2005. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2005/021724ltr.pdf. Accessed October 3, 2014.

[11] MedlinePlus. Partial (focal) seizure. http://www.nlm.nih.gov/medlineplus/ency/article/000697.htm. Accessed October 3, 2014.

[12] Ibid.

[13] Food and Drug Administration. Approval letter to C.P. Pharmaceuticals International C.V. for NDA 21-446/S-010. June 21, 2007. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2007/021446s010ltr.pdf. Accessed October 3, 2014.

[14] Food and Drug Administration. Approval letter to P.F. PRISM C.V. for NDA 021446/S-028. June 20, 2012. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2012/021446s028ltr.pdf. Accessed October 4, 2014.

[15] Pfizer. Package insert for LYRICA (pregabalin). December 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021446s029,022488s008lbl.pdf. Accessed October 4, 2014.

[16] Murphy N, Mockler M, Ryder M, et al. Decompensation of chronic heart failure associated with pregabalin in patients with neuropathic pain. J Cardiac Failure. 2007; 13(3): 227-229.

[17] Pregabalin: Cardiac adverse effects. Prescrire Int. February 2014;23(146):45.

[18] Ibid.

[19] Pfizer. Package insert for LYRICA (pregabalin). December 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021446s029,022488s008lbl.pdf. Accessed October 4, 2014.

[20] Pfizer. Package insert for LYRICA (pregabalin). December 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021446s029,022488s008lbl.pdf. Accessed October 4, 2014.

[21] Arroyo S, Anhut H, Kugler AR, et al. Pregabalin add-on treatment: a randomized, double-blind, placebo-controlled, dose-response study in adults with partial seizures. Epilepsia. 2004;45(1):20-7.

[22] Beydoun A, Uthman BM, Kugler AR, et al. Safety and efficacy of two pregabalin regimens for add-on treatment of partial epilepsy. Neurology. 2005;64(3):475-80.

[23] Elger CE, Brodie MJ, Anhut H, et al. Pregabalin add-on treatment in patients with partial seizures: a novel evaluation of flexible-dose and fixed-dose treatment in a double-blind, placebo-controlled study. Epilepsia. 2005 Dec;46(12):1926-36.

[24] French JA, Kugler AR, Robbins SL, et al. Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures. Neurology. 2003;60(10):1631-7.

[25] Miller R, Frame B, Corrigan B, et al. Exposure-response analysis of pregabalin add-on treatment of patients with refractory partial seizures. Clin Pharmacol Ther. 2003;73(6):491-505.

[26] Food and Drug Administration. FDA requires warnings about risk of suicidal thoughts and behavior for antiepileptic medications. Dec 16, 2008. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm100197.htm. Accessed October 5, 2014.