Lyrica Pregabalin An Objective View

Today's post from Drugdevelopment-technology.com (see link below) looks at the history of Pfizer's Lyrica, or Pregabalin (both names are commonly used. Lyrica was promoted as worthy successor to Gabapentin (Neurontin) in the treatment of neuropathic pain because with its lower dosage (due to greater potency), the side effects are less noticeable. It's worth noting here that Lyrica also has side effects and it very much depends on the individual as to how much they are affected. Apart from this, Lyrica tends to work better for diabetic patients than for people with HIV-related neuropathy. It did better than the placebo in controlling HIV-related neuropathic pain in the short term, but not over the long haul, researchers (from Pfizer themselves)found. Considering its wide usage across the world, you would think that it provides better than average results but every individual is different and several studies have also claimed that Lyrica works no better than a placebo in controlling neuropathic pain. That said, testing the efficacy of this type of drug with HIV-patients who have neuropathy, is notoriously an inexact science. For instance, many people have high expectations when they begin such a treatment and the body increase endorphin levels as a result, which in turn can affect outcomes of tests. Yet it must help large numbers of patients, otherwise it wouldn't be so widely prescribed...(you would think)

Lyrica (Pregabalin) - New Gabapentinoid with Wide,Other
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Drug (Brand/Generic)Lyrica / pregabalin
Company/LicenseePfizer
Therapy ClassAntiepileptic
Product DescriptionGABA analogue
Current IndicationTreatment of neuropathic pain, adjunctive therapy in epilepsy and treatment of generalised anxiety disorder
Market SectorCNS, pain control
Development StatusApproved for neuropathic pain in Europe and the US and additionally for partial seizures in Europe and the US

Developed by Pfizer, pregabalin, marketed under the brand name Lyrica, is a 3-substituted analogue of gamma-amino butyric acid (GABA) and a compound related to Pfizer's hugely successful antiepileptic drug gabapentin (Neurontin).

In July 2004, Pfizer secured Europe-wide approval for Lyrica (pregabalin) for use in the management of peripheral neuropathic pain as well as an adjunctive therapy in the treatment of partial epileptic seizures.

Subsequently, in December 2004 the company gained US Food and Drug Administration (FDA) approval for use of Lyrica (pregabalin) in neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia; making it the first FDA-approved treatment for these neuropathic pain states.

Lyrica (pregabalin) was also reviewed by the FDA as an adjunctive treatment for partial epileptic seizures in adults. In June 2005, the FDA granted approval to market Lyrica for adjunctive treatment of partial epileptic seizures in adults. In June 2007, Lyrica became the first drug to be approved by the FDA for the treatment of fibromyalgia.

"Lyrica is seen as an important successor now that gabapentin is facing the threat of generic competition."

In September 2009, Pfizer was found guilty of misbranding drugs with the aim to defraud or mislead. A subsidiary of the company was promoting four drugs, including Lyrica, for uses not approved by the FDA. Pfizer recieved a fine of $2.3bn. In addition, the company will have to enter a corporate integrity agreement.

A successor to gabapentin

First marketed in 1983, gabapentin (Neurontin) has been one of Pfizer's top performing drugs. Lyrica (pregabalin) is seen as an important successor now that gabapentin is facing the threat of generic competition.

Both drugs share a similar mechanism of action: binding to calcium channels and modulating calcium influx as well as influencing GABergic neurotransmission. This mode of action translates into anti-epileptic, analgesic and anxiolytic effects.

Because it is more potent than gabapentin, Lyrica (pregabalin) achieves efficacy at lower doses. This increases its therapeutic index with respect to gabapentin and should lead to fewer dose-related side effects. Clinical studies with Lyrica (pregabalin) have been carried out on over 10,000 patients worldwide.

Clinical studies with Lyrica (pregabalin) in epilepsy

Gabapentin is approved worldwide for adjunctive treatment of patients with partial epilepsy. Because it is not metabolised (and so does not alter the pharmacokinetics of co-administrated drugs) it is a good candidate for use in combination with other antiepileptic medications.

Clinical studies with oral Lyrica (pregabalin) suggest it is at least as effective as gabapentin as adjunctive therapy in patients refractory to one or more conventional antiepileptic drugs. In large-scale, placebo-controlled studies of 12 weeks' duration, add-on therapy with oral Lyrica (pregabalin) reduced seizure frequency by up to 75%. In these studies doses of Lyrica (pregabalin) ranged from 150mg to 600mg daily.

Clinical studies with Lyrica (pregabalin) in neuropathic pain and anxiety disorder

Neuropathic pain is chronic pain that arises from damage to sensory nerves. It can include:

•Pain arising from trapped or compressed nerves
•Drug-induced nerve damage
•Diabetic neuropathy
•Post-herpetic pain
•Phantom limb syndrome following limb amputation
•Peripheral neuropathy
•Fibromyalgia

Neuropathic pain generally does not respond to treatment with opioid or non-steroidal anti-inflammatory drugs (NSAIDs). At high doses gabapentin has proven effective against neuropathic pain induced by diabetic neuropathy and postherpetic neuralgia. Data from clinical studies show that Lyrica (pregabalin) shares this analgesic effectiveness. Efficacy has been demonstrated in a number of clinical studies, including those in patients with diabetic neuropathy and fibromyalgia. Treatment of neuropathic pain is seen as the drug's leading indication.

"Treatment of neuropathic pain is seen as the drug's leading indication."

A double-blind, placebo-controlled monotherapy study in 529 patients with fibromyalgia, for example, showed that eight weeks' treatment with Lyrica (pregabalin) 150mg to 450mg per day produced significantly greater reductions in pain compared with placebo as well as improving sleep quality and fatigue.

Pain, sleep disturbances and fatigue are core symptoms of fibromyalgia, which has proved an extremely difficult condition to treat.

Data from a series of Phase II and III placebo-controlled clinical studies in over 1,200 patients with generalised anxiety disorder suggested that Lyrica (pregabalin) was effective for this disabling disorder. In comparison with venlafaxine, pregabalin provided more rapid relief of psychic and somatic symptoms.

In comparison with alprazolam (a benzodiazepine), Lyrica (pregabalin) appeared equally effective in reducing somatic symptoms. Overall, these findings showed that Lyrica (pregabalin) combined the benefits of antidepressants and benzodiazepines. It appeared at least as rapid as benzodiazepines against somatic symptoms, while providing more rapid control of psychic symptoms than antidepressants.

Marketing commentary

Once generic manufacture of gabapentin is approved, sales of Pfizer's Neurontin are likely to fall dramatically. Encouraging physicians to switch patients from Neurontin to Lyrica (pregabalin), if approved, will be an important strategy in minimising the impact of generic competition.

Lyrica (pregabalin) is as effective as Neurontin, but at lower doses, which translates to fewer side effects. Thus, it is well placed to capture Neurontin's market share. Through the successful launch of follow-on products, Pfizer has maintained leadership in other CNS areas, such as the market for antidepressants.

http://www.drugdevelopment-technology.com/projects/pregabalin/

Does Pregabalin Lyrica Really Help with Neuropathic Pain

Pregabalin or Lyrica, is one of the most frequently prescribed drugs to help with neuropathic pain. It's an epilepsy/seizure drug that has found a new lease of life in the treatment of neuropathic disorders but there are strong arguments both for and against its usefulness. Many people can't live with the side effects and many people find that it just doesn't work for them. That, set against the people for whom there is a marked improvement, makes it a difficult medication to evaluate. The fact that they're still studying it and that the first American Academy of Neurology guidelines will not emerge until April, 2012, makes you wonder why it is so widely issued by doctors and neurologists. It forms part of what is now accepted as a standard pathway through the possible options for neuropathy patients: somewhere between anti-depressants and morphine! Pregabalin/Lyrica definitely remains a viable option but it's advisable to ask every question that worries you and research as much as you can because at best, you will be suppressing symptoms and not curing them, by using a drug with known side effects. However, for many people if that takes away the pain, then it's worth it. The article comes from emaxhealth.com (see link below).

Pregabalin May Benefit Diabetic Nerve Pain
By Denise Reynolds RD on April 14, 2011

The American Academy of Neurology has issued new guidelines on the most effective treatments for diabetic nerve pain and has found that a seizure drug can treat the neuropathy and improve quality of life for patients with diabetes. The guideline was presented at the American Academy of Neurology’s Annual Meeting in Honolulu.

Diabetic Neuropathy Is Undertreated in the United States
Pregabalin, brand name Lyrica, is an oral medication used for treating pain caused by neurologic diseases as well as seizures. It is also used for treating fibromyalgia. It is believed to work by binding to calcium channels on nerves and possibly modifying the release of neurotransmitters. The US Food and Drug Administration approved pregabalin in December 2004.

Diabetic nerve pain, tingling or burning pain in the hands and feet caused by nerve damage from hyperglycemia, is estimated to affect 16% of the more than 25 million people in the United States living with diabetes. It is believed that about two out of five cases go unreported and untreated.

The recommended initial dose of pregabalin for neuropathic pain is 50 milligrams, three times a day. The dose may be increased to a maximum of 100 mg three times daily after one week. The most common side effects are dizziness, drowsiness, dry mouth, edema, blurred vision, weight gain and difficulty concentrating.

While the evidence is strong that pregabalin is effective in treating diabetic neuropathy, doctors should determine if it is appropriate for their patients on a case-by-case basis. Certain medications can interact with Lyrica, requiring careful monitoring by a physician

The American Academy of Neurology guidelines note that other seizure treatments such as gabapentin and valproate, antidepressants such as venlafaxine or duloxetine, and painkillers are probably also effective. Transcutaneous electric nerve stimulation (TENS) should also be considered as an option for treating diabetic nerve pain.

“We were pleased to see that so many of these pain treatments had high-quality studies that support their use,” said lead guideline author Vera Bril MD FRCP of the University of Toronto. “Still, it is important that more research be done to show how well these treatments can be tolerated over time since diabetic nerve pain is a chronic condition that affects a person’s quality of life and ability to function.”

The AAN guidelines will be released in 2012 and will appear in the April issue of the journal Muscle and Nerve from the American Association of Neuromuscular and Electrodiagnostic Medicine as well as the April issue of PM&R, the journal of the American Academy of Physical Medicine and Rehabilitation.

http://www.emaxhealth.com/1506/pregabalin-may-benefit-diabetic-nerve-pain