Rx Product News: Profile: A Closer Look at New FDA Actions: Lyrica

Dr. Holmberg is a pharmacy residentat the Carl T. Hayden Veterans AffairsMedical Center in Phoenix, Ariz.

Pfizer's Lyrica

After an expedited review, the FDAhas approved Pfizer's Lyrica (pregabalin)for the treatment of fibromyalgia.Before Lyrica's approval, there were noFDA-approved products for the treatmentof fibromyalgia.¹ Lyrica is aSchedule V controlled substance.²

Fibromyalgia is a chronic pain conditionaffecting more than 6 millionAmericans.¹ Its characteristic symptomsinclude pain, fatigue, and sleepproblems.³ Other symptoms may varyover time and include headaches, irritablebowel syndrome, irritable bladder,cognitive and memory problems,temporomandibular joint disorder, pelvicpain, restless legs syndrome, sensitivityto noise and temperature, anxiety,and depression.⁴ While its exactcause is unknown, fibromyalgia isbelieved to be associated with abnormallevels of spinal substance P, thuscausing patients to have an increasedresponse to stimuli that do not usuallycause painful reactions.⁴ Fibromyalgiatends to affect women more than menand usually occurs in adulthood.³

Mechanism of Action

Lyrica's exact mechanism of action isunknown; however, it has been shownto bind to the alpha₂-delta site in thetissue of the central nervous system,which may be responsible for its pain-reliefeffects. Additionally, prolongedapplication of Lyrica has been found toincrease the density of the GABA transporterprotein and to increase the rateof GABA transport.²

Clinical Trials

Lyrica's efficacy for the treatment offibromyalgia was assessed in 2 studies,both of which selected patients withfibromyalgia diagnosed via theAmerican College of Rheumatology criteria.

In Study F1, patients in the Lyricagroup were found to have a significantdecrease in pain, with some patientsexperiencing pain relief as early as 1week after starting treatment.

In Study F2, patients responding totreatment (defined as having both a50% reduction in pain and rating theirpain as "much improved" or "verymuch improved") were randomizedand double-blinded to receive eithertheir treatment dose or placebo andfollowed for up to 6 months. Patientsusing Lyrica had a longer duration untilloss of therapeutic response: 53% ofLyrica patients compared with 33% ofplacebo patients continued the drugand maintained their therapeutic responseuntil Week 26. Lyrica patientsalso experienced a longer time to lossof overall assessment of patient status.²

Dose

The treatment dose for Lyrica is 300to 450 mg daily. Dose titration is as follows:

• 75 mg bid for at least 1 week
• If tolerated for 1 week, increase to150 mg bid
• If further benefit is needed after atleast 1 week, increase to 225 mg bid

In patients with renal dysfunction,the dose should be decreased.

Lyrica can be taken with or withoutfood.²

Safety

Lyrica is contraindicated in patientswith a hypersensitivity to any of itsingredients.

Angioedema has been reported insome patients using Lyrica; shouldangioedemia occur, emergency treatmentshould be sought immediately,and Lyrica should be discontinued.Treatment with Lyrica should bestopped and emergency care shouldbe obtained if hypersensitivity reactions,such as hives, dyspnea, andwheezing occur. Patients with seizuredisorder may experience increasedseizure frequency if Lyrica is suddenlystopped. Lyrica has been associatedwith peripheral edema and should beused with caution in patients usingconcomitant thiazolidinedione antidiabeticagents. Weight gain, increasedcreatine kinase levels, decreasedplatelets, and P-R interval prolongationhave been noted. Patients using Lyricamay experience dizziness or somnolencethat may impair their ability todrive or operate machinery.

Lyrica is a Pregnancy Category Cdrug. Patients who are breast-feedingshould discontinue either treatmentwith Lyrica or breast-feeding.²

Side Effects

In clinical trials, 7% of patients usingLyrica experienced blurred vision.Other side effects associated withLyrica included dizziness, somnolence,dry mouth, edema, weight gain, constipation,euphoric mood, balance disorder,increased appetite, and abnormalthinking.¹

References

• Pfizer's Lyrica receives FDA approval for fibromyalgia based on expedited review [press release]. June 21, 2007. Available at: www.pfizer.com/news/pfizer_press_releases.jsp. Accessed August 2007.
• Lyrica prescribing information. Available at: www.pfizer.com/pfizer/download/uspi_lyrica.pdf. Accessed August 2007.
• FDA approves first drug for treating fibromyalgia [press release]. June 21, 2007. Available at: www.fda.gov/bbs/topics/NEWS/2007/NEW01656.html. Accessed August 2007.
• American College of Rheumatology. Fibromyalgia. Available at: www.rheumatology.org/public/factsheets/fibromya_new.asp. Accessed August 2007.