Update on New Diabetic Peripheral Neuropathy Treatment

Those in diabetes care need to be aware of Lyrica’s (pregabalin, Pfizer Inc.)dosages, special considerations, and side effects. Lyrica is a central nervous system-active drug for neuropathic pain associated with diabetic peripheral neuropathy (DPN) and postherpetic neuralgia (PHN).

Recommended Dosage: PHN: 150-300 mg per day, in two or three doses; can be increased up to 600 mg per day, based on tolerability. DPN: 300 mg per day, given in three doses, according to Pfizer.

Special Considerations: In trials, side effects were tolerable and similar to those with other CNS drugs; sedation and dizziness were among the most common, said Brett R. Stacey, M.D., one of the investigators. Lyrica won’t be available until the Drug Enforcement Administration decides on the drug’s controlled substance category. The company expects Lyrica will be in a category with lower potential for misuse or abuse than other controlled substances.

Comment: Approval was based on six studies of more than 1,000 patients with PHN or DPN. Lyrica provided quick, clinically meaningful pain reduction. In DPN trials, about half the patients had at least a 50% response rate; in PHN trials, response rates were lower but were still “impressive,” said Dr. Stacey, medical director of the comprehensive pain center at Oregon Health and Science University, Portland. For both conditions, “the time course to pain relief will be much quicker” than with treatments such as tricyclic antidepressants, which must be started at a low dose.

Like gabapentin, which is used for a variety of pain syndromes, Lyrica binds to a calcium channels subunit, resulting in effects including pain relief for these two conditions and anticonvulsant activity. (It is also under FDA review for a seizure indication.) Lyrica “appears to bind more avidly” than gabapentin, and pain relief can begin the day after treatment starts, he added. Lyrica’s narrow dose range makes it easier to prescribe than gabapentin, which has a “huge” dose range, said Dr. Stacy, who has done research for Pfizer and has been a consultant to the company for both drugs.

Side Effects: The safety of Lyrica was established in over 9,000 patients. In all clinical trials, adverse events were mild to moderate. The most common side effects associated with Lyrica compared with placebo included dizziness, somnolence, dry mouth, peripheral edema, blurred vision, weight gain and difficulty with concentration/attention. The discontinuation rate due to side effects was low. Lyrica is expected to be classified as a controlled substance in a category with lower potential for misuse or abuse relative to controlled substances in other categories.

Many drugs are used off-label to treat these conditions, but Lyrica is only the second FDA-approved drug for DPN-associated pain; Cymbalta (duloxetine), a selective serotonin norepinephrine reuptake inhibitor, was approved in September for this use. Lyrica is the third drug approved for PHN; the others are gabapentin and the 5% lidocaine patch.
Synopsis of Studies submitted to FDA

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FACT:
According to a retrospective look at UKPDS, delayed progression from glucose intolerance to type 2 diabetes in high-risk individuals with glucose intolerance has been demonstrated with troglitazone, metformin and acarbose. However, intensive lifestyle intervention can be more effective than drug therapy, at least in the setting