Natural Pain Relief drug - Eazol

Eazol can reduce the level of prostaglandins in your body. These compounds can cause the aches, pain and inflammation that make life miserable for so many people. Eazol helps to relax your muscles and to reduce swelling. It improves blood flow to areas such as the joints. The ingredients of Eazol work with each other, so that they're even more effective together than they are alone. And, they don't cause the sort of gastrointestinal irritation that can occur when you use many other kinds of pain reliever!

Active Ingredients:

White Willow (Salix species) (bark): The bark of the stately white willow tree (Salix alba) has been used in China for centuries as a medicine because of its ability to relieve pain and to lower fevers. Early settlers in America found Native Americans gathering bark from indigenous willow trees for similar purposes. The active ingredient in white willow is salicin, which the body converts into salicylic acid. The first aspirin (acetylsalicylic acid) was made from a different herb containing salicin�meadowsweet�but works in essentially the same way. All aspirin is now chemically synthesized. It's not surprising, then, that white willow bark is often called "herbal aspirin". Although white willow is the species of willow tree most commonly used for medicinal purposes, other salicin-rich species are employed as well, including crack willow (Salix fragilis), purple willow (Salix purpurea), and violet willow (Salix daphnoides). These all may be sold under the label of willow bark.


Health Benefits: The salicylic acid in white willow bark lowers the body's levels of prostaglandins, hormonelike compounds that can cause aches, pain, and inflammation. While white willow bark takes longer to begin acting than aspirin, its effect may last longer. And, unlike aspirin, it doesn't cause stomach bleeding or other known adverse effects. White willow bark may help to relieve acute and chronic pain, including arthritis pain, headache, back and neck pain, muscle aches, and menstrual cramps. The effectiveness of white willow bark for easing these and other types of discomforts results from its power to lower prostaglandin levels. Some arthritis sufferers taking white willow bark have experienced reduced swelling and inflammation, and have eventually achieved increased mobility in the back, knees, hips, and other joints.

Lobelia (Lobelia inflata):This herb is named after the botanist Matthias de Lobel, a native of Lille, France, who died in London in 1616. The common name Lobelia also includes the species Lobelia siphilitica, Lobelia cardinalis and Lobelia chinensis, all of which are used interchangeably with Lobelia inflata. Lobelia is native to North America, and was both chewed and smoked by Native Americans. Lobelia root was used by the Iroquois Indians to treat syphilis, which is the source of the species name "siphilitica".

Health Benefits: One of the most useful muscle relaxants, Lobelia is rich in vitamin A, vitamin C, and manganese. An active ingredient in the lobelia plant, lobeline, stimulates nerves in the central nervous system. Lobelia is considered beneficial for treating mild depression, reducing inflammation and pain, easing muscle tension and calming the nerves. The primary chemical constituents of lobelia include piperidine alkaloids (lobeline, isolobeline), lobelic acid, chelidonic acid, glycoside (lobelacrin), essential oil, resins, and fats. The activity of Lobelia is dependent upon the liquid alkaloid, lobeline. Lobelia also contains gum, resin, chlorophyll, fixed oil, lignin, salts of lime and potassium, and ferric oxide. Lobelia may be used in many conditions in combination with other herbs to further their effectiveness.

Boswellia (standardized to contain 55% Boswellic Acid) (Boswellia serrata) (leaf): Boswellia, also known as boswellin or "Indian frankincense," comes from the tree Boswellia serrata, that grows in the dry hills of India. For centuries, traditional Indian healers have taken advantage of the anti-inflammatory properties of the tree bark's gummy resin, called salai guggal. Modern preparations made from a purified extract of this resin and packaged in pill or cream form are used to reduce inflammation associated with osteoarthritis and rheumatoid arthritis. Unlike conventional NSAIDs (nonsteroidal anti-inflammatory drugs) such as ibuprofen�the accepted treatments for joint inflammation�boswellia doesn't seem to cause stomach irritation. It also may be effective for back pain and certain chronic intestinal disorders.

Health Benefits: Research has identified specific active anti-inflammatory ingredients in this herb, which are commonly referred to as boswellic acids. In animal studies, these acids have been shown to reduce inflammation significantly in several ways. Boswellic acids deter inflammatory white cells from infiltrating damaged tissue. They improve blood flow to the joints. They also block chemical reactions that set the stage for inflammation to occur in chronic intestinal disorders such as Crohn's disease and ulcerative colitis. Boswellia may help to ease symptoms of osteoarthritis and rheumatoid arthritis. Boswellia can be taken internally as well as applied topically to affected joints to relieve inflammation associated with these joint disorders. This may lessen morning stiffness and increase joint mobility. In a study of 175 patients with rheumatic disorders such as rheumatoid arthritis, 122 participants experienced reduced stiffness and inflammation two to four weeks after starting on a boswellia regimen. Boswellia's anti-inflammatory properties can help to reduce aching and stiffness, especially when associated with low back pain. Although research indicates that boswellia is best taken orally for this purpose, creams appear to be soothing as well. Boswellia also appears to reduce the inflammation associated with ulcerative colitis and Crohn's disease, both painful intestinal disorders. It seems to accomplish this without the risk of further gut irritation associated with many conventional pain relievers. In a 1997 study of ulcerative colitis sufferers, 82% of those who took boswellia extract (350 mg three times daily) experienced a complete remission of their disease.

How Vioxx is changing US drug regulation

erck and Co now faces more than 6000 lawsuits involving the COX2 inhibitor rofecoxib, marketed as Vioxx. But no matter how these legal battles are resolved, the cases are already having an impact on how the pharmaceutical industry and government regulators do business. Todd Zwillich reports.

Merck and Co celebrated victory earlier this month after a New Jersey jury ruled that the company's anti-inflammatory drug rofecoxib (Vioxx) did not cause the heart attack of a 60-year-old postal worker. The verdict evened the score for the pharmaceutical giant, which in August lost a similar trial in Texas and was asked to pay US$253 million compensation.

The August case is under appeal, and Texas law will cut the award by 90%. But the company is just at the beginning of a series of Vioxx-based legal battles, which are expected to continue for years to come.

Plaintiffs have filed around 6400 lawsuits claiming that the cyclo-oxygenase 2 (COX2) inhibitor—which was pulled from the market in Sept, 2004—caused their heart attacks or strokes. Merck's overall liability in the lawsuits could reach $20–35 billion, according to analysts.

The company has vowed not to make any settlements, and instead promises to fight every case in court. It has already set aside $675 million for the effort.

But Vioxx's fallout goes well beyond Merck and its ledgers. Manufacturers facing mounting political pressure have now agreed to scale back advertising—an activity once staunchly defended by the industry. Meanwhile, the US Food and Drug Administration (FDA) has taken what some see as a defensive posture designed to avoid another safety debacle.

Merck is set to begin defending its third case at the end of November. Lawyers for the widow of Richard Irvin will try to show that the drug was responsible for the man's sudden cardiac death and that Merck officials knew of the risk while marketing the drug.

The case will be the first to reach federal court and will also test uncharted scientific ground. Irvin's widow claims that the drug caused his death after only a month of use. That is far shorter than the 18 months of average use it took for increases in cardiovascular risks to show up in Merck's trials.

“The autopsy shows the location of the clot and shows he had no prior significant heart disease problems. That makes our job easier”, Jere Beasley, the attorney representing the widow, Evelyn Irvin Plunkett, said in an interview.

Beasley points to anecdotal warnings Merck received as early as 1997 associating early use of the drug with cardiac death.

The company maintains that rofecoxib could not have caused Irvin's death. Increased risk of cardiac death in the Merck-directed APPROVe placebo-controlled trial did not reach statistical significance until 30 months of use, Bruce Kuhlik, Merck's vice president and associate general counsel, told The Lancet.

Merck stands by its pledge to avoid settling any cases. “We're committed to defending the cases on an individual basis, based on the science behind Vioxx and the individual risk factors that each individual patient has”, Kuhlik says.

Even if the plaintiff's strategy proves successful, it remains unclear what will be the impact on the overall dispensation of suits against Merck. 2 weeks before the federal trial opened, the New Jersey judge overseeing about half the total Vioxx caseload told attorneys that the next string of trials will focus only on plaintiffs who used the drug for 18 months or more.

The New Jersey victory proved to would-be plaintiffs that their suits against Merck will not be easy to win, says Robert Rabin, an expert in mass torts at Stanford Law School in California. The company is unlikely to ultimately stick to its pledge to fight each case, he says. At the same time, it pays in the short term for Merck to be as combative as possible.

“Sixty-four hundred cases are not going to be decided at trial individually. But it's not just 6400 cases if they started settling. Who knows how many other cases that would generate”, Rabin told The Lancet.

But the lawsuits reflect concerns over prescription-drug safety that go well beyond the courtroom. Other manufacturers are also reacting to allegations that they were too cavalier with safety in the rush to get promising new drugs to market.

As the Texas jury was nearing judgment against Merck in August, the Pharmaceutical Research and Manufacturers of America, the industry's main trade group, committed companies to withhold consumer advertisements of new drugs until physicians have been sufficiently educated about risks and benefits.

Pfizer Inc, the maker of COX2 drug celecoxib, marketed as Celebrex, and valdecoxib, marketed as Bextra, volunteered to ban consumer commercials for the first 6 months of drug sales. Bristol-Myers Squibb has said it will impose its bans for a year. Both were shorter than a 2-year moratorium on direct-to-consumer advertisements for new drugs called for by Senate Majority Leader and physician Bill Frist.

The major advantage of the COX2 inhibitors is their reduced risk of causing gastro-intestinal irritation and bleeding compared with non-selective COX inhibitors. But company advertisements were widely criticised for promoting the COX2 drugs to millions of patients who were not at risk for these side-effects. COX2 inhibitors do not offer an analgesia advantage over other anti-inflammatory pain killers.

“They've clearly gotten the message and tried to back away from (consumer advertising) discreetly”, says Alistair Wood, a professor of medicine and pharmacology at Vanderbilt Medical School in Nashville, TN, who chaired a 3-day series of hearings on COX2 safety in February.

Companies are also sensing that the FDA has reacted by making stricter demands on manufacturers, analysts say. Reports of increased suicidal ideation in patients taking antidepressants, defects in cardiac pacemakers, and political fury over the agency's unusual handling of a request to make an emergency contraceptive available without a prescription have all spurred the agency to avoid more mistakes, argues Michael Krensavage, a drug industry analyst. “It's a lot riskier for these companies to play games now than it used to be”, he says.

Krensavage says the new approach was in evidence in October when the agency demanded more safety data from Bristol-Myers Squibb and Merck before agreeing to approve muraglitazar, a jointly-developed type 2 diabetes drug to be marketed as Pargluva. The agency was concerned about data suggesting the drug could double cardiovascular risk, despite an 8-to-1 advisory committee vote backing the drug's approval only a month before.

Others expect any increased scrutiny to be temporary. That was the case in 1997 after fentermine-phenfluramine, the weight-loss combination known as fen-phen, was pulled from the market shortly before a wave of lawsuits connecting it to cardiac death, says Les Funtleyder, a health care analyst with the financial firm Miller Tabak & Co.

“Post fen-phen, things tightened up for about 18 months”, Funtleyder says. “This regulation tends to be cyclical. They'll tend to get tighter for a while and after we've gone a few years without a major safety scandal, they'll go laissez-faire again”, he says.

Steven Galson, director of the FDA's centre for drug evaluation and research, says that companies have become concerned about more FDA scrutiny and that officials may be looking more closely at industry applications. But he denied in an interview that the agency's decision-making process has changed.

“You can't avoid some of FDA's reviewers taking a harder look at safety info but that doesn't mean were going to be stricter in our safety decisions”, Galson said. “I object to the notion that there's any evidence that we've become stricter in the last few months.”

Kuhlik maintains that Merck has not altered the way it interacts with FDA. “I just don't see that changing”, he says.

The FDA has reacted in other, more obvious ways. The agency has vastly increased the amount of safety-report information it shares with the press and the public, regularly publicising minor drug-label changes and other safety information. An independent review of how the agency monitors drugs already on the market is underway, and over the summer the agency created a new board to help monitor drug safety.

Wood, who in 2002 was a candidate to take over as FDA commissioner, takes a dim view of the agency's recent moves. He likens the organisational changes to “shuffling the deck chairs on the Titanic” and says that the FDA should instead lower its threshold for compelling companies to conduct safety trials involving already-common side-effects like the heart attacks suspected with Vioxx. “The place to make the change is the FDA, not to ratchet up the tort system”, Wood says.

Safety concerns at the FDA

The US Food and Drug Administration is in crisis. Under fire for its record on drug safety, brought to a head when Merck voluntarily withdrew rofecoxib in September, 2004, and suffering from prolonged lack of leadership, the FDA is in a sorry state.

Three decisions in the past few weeks were heralded as cause for optimism. On Feb 14, President Bush nominated Lester Crawford, the acting commissioner of the FDA, to become its permanent commissioner. An advisory panel spent 3 days last week hearing evidence on the efficacy and safety of the COX-2 inhibitors rofecoxib (Vioxx), valdecoxib (Bextra), and celecoxib (Celebrex). And on Feb 15, the FDA announced that it was creating a Drug Safety Oversight Board.

Lester Crawford has been acting commissioner or deputy commissioner to the FDA for almost 3 years under the Bush administration. The permanent post has been vacant since March, 2004, when the previous chief, Mark McClellan, left after only 17 months. Crawford is a veterinarian with a PhD in pharmacology. It is during his reign as acting commissioner that concern over drug safety has reached a head. Sidney Wolfe, a long-time critic of the FDA and a director at Public Citizen, a consumer advocacy group, told The Lancet that Crawford had done a “terrible job”, with a poor record on drug safety issues, failing to warn adequately about the cardiovascular risks of rofecoxib. “Crawford won, so the American public loses”, said Wolfe on Crawford's nomination as FDA chief. Crawford has shown repeatedly that he lacks the determination to strengthen the weak regulatory culture within the FDA. He has failed to protect agency scientists who try to speak openly about drug safety concerns. And he has refused to recognise that his primary duty is to protect the public, not to facilitate the entry of inadequately tested medicines onto the market.

The FDA took the unusual step of holding a joint public meeting of its Arthritis Advisory Committee and its Drug Safety Risk Management Advisory Committee between Feb 16 and 18. The aim was to discuss the overall benefit to risk considerations for the three COX-2 selective non-steroidal anti-inflammatory drugs currently approved in the USA. The conclusion of the panel was that the potential benefits outweighed the risks. Support for marketing was stronger for celecoxib (with 31 panellists in favour, and one against) than for valdecoxib (17 in favour, 13 against) or rofecoxib (17 for, 15 against). All three drugs should, said the panel, be marketed as painkillers accompanied by strong warnings of the risks, including the cardiovascular risks, which the panel concluded were likely to be a class effect and not unique to rofecoxib. The FDA usually follows its committees' advice. When the FDA does issue its conclusions, which may not be for a few weeks, clear guidance on which patients are most likely to benefit, and least likely to be harmed, and on dose and duration is needed, assuming the data are available.

Announcing the creation of the Drug Safety Oversight Board, Crawford and Health and Human Services Secretary Mike Leavitt said that the board would consist of scientists drawn from throughout the federal government. The board will advise on the management of drug safety issues within the Center for Drug Evaluation and Research. It will not have the independent power to force the withdrawal or relabelling of drugs, but can only advise the FDA. The board will make its conclusions public via a new Drug Watch internet site, which will allow discussion of emerging or potential safety issues before the FDA has reached conclusions that would prompt regulatory action. In addition, changes at the FDA will allow information about adverse effects of drugs to be collated from databases, including those at Medicaid and other government or private health plans, and will increase the number of FDA-approved fact sheets that patients receive with their prescriptions. However, analysing adverse event data held on large databases will cost millions of dollars each year, yet no additional funding has been provided.

Until now, it has been the remit of the Office of Drug Safety at the FDA to monitor adverse events. But with a staff of around 100 to analyse the miscellaneous reports sent in by doctors and drug companies, and a reporting structure submerged within the FDA's drug review division, the Office of Drug Safety has neither the power nor the independence needed to reliably detect drug side-effects and to take action to protect patients.

This solution to the problem of monitoring drug safety is flawed. The new Drug Safety Oversight Board is a hurriedly put together substitute to fundamental change in the structure and power of the Office of Drug Safety. What is needed is an Office of Drug Safety with increased staff, and the same power and political clout as the Office for New Drugs. Monitoring drug safety can be done within the FDA if there are no ties with the division that is responsible for approving new drugs, and if enough money is given to fund database analyses. In addition, the Bush administration must grant the FDA greater legal authority to demand that manufacturers conduct postmarketing surveillance or give the FDA the resources to fund its own drug-surveillance studies. Creating a board with only advisory powers on an issue as important as drug safety is unacceptable.

“The FDA is an icon of trust, a certifier of safety, an enabler of innovation and a repository of information”, said Leavitt when announcing the new Drug Safety Oversight Board. If only all that were the case. He continued, “We will keep the promise of the FDA brand by putting in place more rigorous oversight and collecting and sharing important and emerging information about drug safety and effectiveness”. What is in place or being created so far is, unfortunately for the US public, inadequate to monitor drug safety. What is needed is an FDA chief with the foresight and ability to change a lumbering organisation, armed with the legal framework to achieve an effective drug safety monitoring system, and the power to then act promptly when safety concerns arise.