For Which Neuropathies Is Lyrica Really Suitable

Today's post is a Pfizer Press release (see link below) concerning Lyrica being prescribed for a specific form of neuropathy. The American FDA has approved its use for neuropathy associated with spinal cord injuries (for which there was no approved treatment before). It's a Pfizer press release, so it positively glows with pride at the achievement, yet they have withdrawn the drug for treatment of HIV-related and other neuropathies. It doesn't make sense. The pain receptors that Lyrica targets are much the same for most forms of neuropathy, yet some are considered suitable for Lyrica treatment and others not. It is still widely prescribed for HIV-related neuropathy across the world, as different medical authorities try to decide what to do about it and what the truth is. Considering the court cases Pfizer have had to face concerning the side effects of Lyrica, it would be advisable to talk carefully with your doctor before starting a course of this drug - the possible side effects shouldn't be underestimated (more articles about this subject in the list on the right of the blog). Maybe Pfizer should consider explaining the situation in simple terms to the patients themselves?

FDA Approves Lyrica For The Management Of Neuropathic Pain Associated With Spinal Cord Injury Based On Priority Review

June 21, 2012

First and Only Treatment Option Approved in the U.S. for Pain Condition Affecting 40 Percent of Spinal Cord Injury Patients

NEW YORK--(BUSINESS WIRE)--Pfizer Inc. (NYSE: PFE) announced today that the U.S. Food and Drug Administration (FDA) approved the use of Lyrica^® (pregabalin) capsules CV for the management of neuropathic pain associated with spinal cord injury. Lyrica received a priority review designation for this new indication from the FDA. More than 100,000 patients – approximately 40 percent of the 270,000 patients with spinal cord injury in the United States - suffer from this chronic, complex pain condition. Neuropathic pain associated with spinal cord injury can be severely debilitating and may significantly hinder rehabilitation and the ability to regain function.
  
“This milestone represents an important opportunity for physicians to more effectively manage the debilitating neuropathic pain that often accompanies spinal cord injury,” said clinical study investigator Diana Cardenas, MD, MHA, professor and chair, department of rehabilitation medicine, University of Miami Miller School of Medicine and chief of service for rehabilitation medicine and medical director of Jackson Rehabilitation Hospital, Miami, Florida. “Given the clinical challenges of investigating neuropathic pain in this patient population, any advancements in treatment are welcome by physicians and patients alike.”
  
An estimated 12,000 new spinal cord injury patients are diagnosed in the U.S. each year. There are a wide variety of causes for spinal cord injury, including traumatic and non-traumatic causes. Traumatic causes may include motor vehicle accidents, violence, falls and sports injuries. In these instances, a spinal cord injury typically begins with a sudden, traumatic blow to the spine that fractures or dislocates vertebrae. The damage begins at the moment of injury when displaced bone fragments, disc material, or ligaments bruise or tear into spinal cord tissue. Non-traumatic causes may involve congenital and developmental abnormalities, genetics and metabolism, infections and inflammation, removal of a benign spinal tumor and spinal cord ischemic stroke.
  
Neuropathic pain can be experienced above, at or below the level of the spinal cord injury, and is typically not confined to one area in the body. Approximately one-third of spinal cord injury patients report below-level neuropathic pain that is severe or excruciating. Patients may experience neuropathic pain associated with spinal cord injury as early as two weeks after injury and it may persist for up to 25 years.
  
“Until now, no FDA approved treatment options were available in the U.S. for people with neuropathic pain associated with spinal cord injury, a condition which can be extremely disabling,” said Steven J. Romano, MD, senior vice president and head, medicines development group, Global Primary Care Business Unit, Pfizer. “The approval of Lyrica for this indication is a significant milestone, exemplifying Pfizer’s commitment to pursue scientific advancements that address unmet medical needs.”
  
About Lyrica Phase 3 Clinical Studies
The FDA approval is based on two randomized, double-blind, flexibly dosed (150–600 mg/day), placebo-controlled Phase 3 trials, which enrolled 357 patients. Among other medications, patients were allowed to continue taking other pain medications, including NSAIDs, opioids and non-opioids. The population of one study consisted of traumatic spinal cord injury patients. The population of the other study consisted of traumatic spinal cord injury patients and patients who had injury to the spinal cord from non-traumatic causes: e.g., removal of a benign spinal tumor or spinal cord ischemic stroke (five percent of patients).
  
The primary finding in these studies was that Lyrica significantly reduced neuropathic pain associated with spinal cord injury from baseline throughout the duration of the studies (12 weeks and 16 weeks, respectively), compared to placebo. In addition, more patients receiving Lyrica showed a 30 percent and 50 percent reduction in pain than did patients receiving placebo. In some patients, the reduction in pain with Lyrica was significant as early as week one and continued throughout the duration of the trials.
  
The most common adverse events in these trials in patients receiving Lyrica were somnolence, dizziness, dry mouth, fatigue and peripheral edema.
  
About Lyrica
Lyrica is currently approved for various indications in 120 countries and regions globally. In the United States, Lyrica is indicated for diabetic nerve pain, post herpetic neuralgia (pain after shingles), fibromyalgia, neuropathic pain associated with spinal cord injury and partial onset seizures in adults with epilepsy who take one or more drugs for seizures. Antiepileptic drugs (AEDs) including Lyrica increase the risk of suicidal thoughts or behavior in patients taking AEDs for any indication.
There have been post-marketing reports of angioedema and hypersensitivity with Lyrica. Treatment with Lyrica may cause dizziness, somnolence, dry mouth, edema and blurred vision. Other most common adverse reactions include weight gain, constipation, euphoric mood, balance disorder, increased appetite and thinking abnormal (primarily difficulty with concentration/attention).
For Lyrica prescribing information, please visit www.lyrica.com.
  
Pfizer Inc.: Working together for a healthier world^®
At Pfizer, we apply science and our global resources to improve health and well-being at every stage of life. We strive to set the standard for quality, safety and value in the discovery, development and manufacturing of medicines for people and animals. Our diversified global health care portfolio includes human and animal biologic and small molecule medicines and vaccines, as well as nutritional products and many of the world’s best-known consumer products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as the world’s leading biopharmaceutical company, we also collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us. To learn more about our commitments, please visit us at www.pfizer.com.

http://www.pfizer.com/news/press_releases/pfizer_press_release.jsp?guid=20120621005572en

Will Generic Pregablin Lyrica Be Any Better For Neuropathy Patients

Today's post from psnc.org.uk (see link below) is a British view and advice to pharmacists on the changing status of Lyrica, as Pfizer's patent has now run out and generic versions will be coming onto the market. Pfizer in their wisdom, have decided to maintain a Lyrica patent for patients with neuropathy, at least until July 2017. This will effectively prevent other companies from bringing out a generic version until that date. Now in 2013, Pfizer were quite clear that pregabalin (Lyrica) was in their own eyes unsuitable for diabetes and HIV-related neuropathy patients. This was mainly due to adverse study outcomes and many court cases relating to side effect issues. The point is: what's changed? the answer: probably nothing: they still won't approve Lyrica for HIV and diabetes neuropathy patients and the FDA backs that up completely. So is this just a corporate move to prevent rivals from bringing generic Lyrica to the market too quickly? More importantly for neuropathy patients; will generic pregabalin (lyrica) be any more effective and any less dangerous for patients in the future. We'll have to wait and follow the recommendations for the US FDA and similar authorities across the world but until then, if your doctor is still prescribing Pregabalin (Lyrica) (generic or not) for your neuropathic problems, you need to have a serious discussion as to whether this is in fact, the best option.

Pregabalin (Lyrica) – Licensing differences between Lyrica and Generic
January 29, 2015

Pregabalin (Lyrica) patent is changing and generic pregabalin is becoming available. The NPA have issued advice (shown below) regarding the licencing of the products.

The NPA have also informed us that are also in the process of discussing this issue with the MHRA and Pfizer.

Dear Pharmacist
You may find in the coming months that generic pregabalin is available to order. I would like to highlight to you that although the patent for pregabalin expired in July 2014, this patent expiry related to the use of pregabalin in epilepsy and generalised anxiety disorder; Pfizer will retain a patent for the use of pregabalin in the treatment of peripheral and central neuropathic pain in adults until July 2017.
This means that until July 2017, generic manufacturers of pregabalin will only be able to obtain a licence for pregabalin for use in epilepsy and/or generalised anxiety disorder and Lyrica, Pfizer’s branded product, will remain the only product licensed for use in pain as well as epilepsy and generalised anxiety disorder.

Pfizer has indicated that it will contest any challenges to the patent for pain.

To avoid any possible patent infringement by pharmacists, steps will need to be taken to ensure that where generic pregablin is requested on a prescription the correctly licensed product is supplied. This may mean contacting the prescriber and establishing the indication and requesting that the prescription is amended and ordered by brand as Lyrica if necessary.

Although generic pregabalin is unlikely to differ clinically from the branded Lyrica, supplying the generic version of pregabalin for neuropathic pain may have the following implications for pharmacists:
Generic pregabalin preparations will not include information relating to neuropathic pain in the patient information leaflet and pharmacists will be supplying a product off-licence
Supplying generic pregabalin for neuropathic pain would not be in line with Medicines and Healthcare products Regulatory Agency’s risk hierarchy guidance for the supply of unlicensed medicinal products, which states that a UK-licensed product should always be supplied for the correct licensed indication
Using generic pregabalin for neuropathic pain may be deemed by Pfizer to be a patent infringement by all parties concerned, including the prescriber and the supplying pharmacist

Currently, reimbursement for NHS prescriptions for pregabalin is based on Lyrica. This may change when generic versions become available meaning that pharmacists may not be correctly reimbursed where Lyrica is supplied against a generically written prescription for pregabalin. I advise that where generic prescriptions for pregabalin are received, the prescriber is contacted to ascertain the indication. Where the indication is for neuropathic pain, the prescription should be returned to the prescriber for amendment to Lyrica. Prescriptions for pregabilin for epilepsy or generalised anxiety disorder can be dispensed with either Lyrica or appropriately licensed generic versions.

When supplying pregabalin for the treatment of epilepsy, pharmacists should also consider MHRA guidance issued in 2013 regarding the generic prescribing of antiepileptics. The guidance states that pregabalin does not generally need to be prescribed by brand for the treatment of epilepsy unless there are specific concerns such as patient anxiety and a risk of confusion or dosing errors.

For further information on this or any other query please contact the NPA Pharmacy Services Team on 01727 891 800 / 08447 364 201
or email pharmacyservices@npa.co.uk .

http://psnc.org.uk/sunderland-lpc/our-news/pregabalin-lyrica-licensing-differences-bewteen-lyrica-and-generic/

Are Neurontin And Lyrica Really The Best Options For Neuropathic Pain

Today's post from wellnessresources.com (see link below) is an out and out attack on Lyrica (pregabalin) and neurontin as drugs for neuropathic symptoms. However, it has to be said, it's now wildly out of date. Nevertheless, the prophetic warnings in the article have been borne out. It was written in 2009 and since then the FDA has issued strong warnings about Lyrica...and Pfizer (the manufacturers) have themselves withdrawn positive advice for its use in tackling diabetic and HIV-related neuropathy. Yet, these drugs are still universally popular and widely prescribed by doctors. Is this a case of heavy promotion by the drug company, or a refusal to face the facts on the part of health professionals? Unfortunately, Lyrica is one of those drugs that seems to have a multi-function and is prescribed for all sorts of nerve problems. It is so deeply entrenched in the lexicon of nerve problem treatments that subsequent warnings, law suits and withdrawals of support from its own maker, have had little effect on its popularity. If your doctor or neurologist wants to prescribe Lyrica for you, it may be time to pose some serious questions, especially if your neuropathy stems from diabetes or HIV-related causes. There are alternatives which may be safer for you in the long run. More articles on this subject can be found by typing in 'Lyrica' in the search box to the right of this blog.

Neurontin and Lyrica are a Death Sentence for New Brain Synapses
Byron J. Richards, Board Certified Clinical Nutritionist Wednesday, October 14, 2009

Neurontin and its newer more potent version, Lyrica, are widely used for off-label indications that are an outright flagrant danger to the public. These blockbuster drugs were approved for use even though the FDA had no idea what they actually did in the brain. A shocking new study shows that they block the formation of new brain synapses1, drastically reducing the potential for rejuvenating brain plasticity – meaning that these drugs will cause brain decline faster than any substance known to mankind.

The problem of these drugs is compounded by their flagrant illegal marketing. Neurontin was approved by the FDA for epilepsy back in 1994. The drug underwent massive illegal off-label promotion that cost Warner-Lambert 430 million dollars (the very first big fine for off-label promotion). The drug is now owned by Pfizer. Pfizer also owns Lyrica, a super-potent version of Neurontin. It has been approved by the FDA for various types of pain and fibromyalgia. Lyrica is one of four drugs which a subsidiary of Pfizer illegally marketed, resulting in a $2.3 billion settlement against Pfizer.

Even though the marketing of these drugs has been heavily fined, they continue to rack up billions in sales from the off-label uses. Doctors use them for all manner of nerve issues because they are good at suppressing symptoms. However, such uses can no longer be justified because the actual mechanism of the drugs is finally understood and they are creating a significant long-term reduction in nerve health.

The researchers in the above study try to downplay the serious nature of the drugs by saying “adult neurons don’t form many new synapses.” That is simply not true. The new science is showing that brain health during aging relies on the formation of new synapses. Even these researchers managed to question the common use of these medications in pregnant women. How is a fetus supposed to make new nerve cells when the mother is taking a drug that blocks them?

These are the kind of situations the FDA should be all over. As usual, the FDA is sitting around pondering a suicide warning for Lyrica while its off-label uses include bi-polar disorder and migraine headaches. The FDA is likely to twiddle its thumbs for the next decade on the brain damage issue. Consumer beware.

http://www.wellnessresources.com/freedom/articles/neurontin_and_lyrica_are_a_death_sentence_for_new_brain_synapses/

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
News, views and contacts from the global Drug development industry

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