The Food and Drug Administration approved updated labeling for the Ortho Evra contraceptive patch to warn healthcare providers and patients that this product exposes women to higher levels of estrogen than most birth control pills. Ortho Evra was the first skin patch approved for birth control.
It is a weekly prescription patch that releases ethinyl estradiol (an estrogen hormone) and norelgestromin (a progestin hormone) through the skin into the blood stream. FDA advises women to talk to their doctor or healthcare provider about whether the patch is the right method of birth control for them.
Furthermore, women taking or considering using this product should work with their health care providers to balance the potential risks related to increased estrogen exposure against the risk of pregnancy if they do not follow the daily regimen associated with typical birth control pills. Because Ortho Evra is a patch that is changed once a week, it decreases the chance associated with typical birth control pills that a woman might miss one or more daily doses.
The addition of this new warning is a result of FDA’s and the manufacturer’s analysis directly comparing the levels for estrogen and progestin hormones in users of Ortho Evra with those in a typical birth control pill. In general, increased estrogen exposure may increase the risk of blood clots. However, it is not known whether women using Ortho Evra are at a greater risk of experiencing these serious adverse events.
The new bolded warning specifically states that women who use Ortho Evra are exposed to about 60 percent more total estrogen in their blood than if they were taking a typical birth control pill containing 35 micrograms of estrogen. However, the maximal blood level of estrogen (peak blood levels) is about 25% lower with Ortho Evra than with typical birth control pills. While the estrogen level with the patch remains constant for one week until the patch is removed, the peak blood levels with a daily birth control pill rapidly declines to levels that are lower than on the Orthro Evra.
FDA is continuing to monitor safety reports for the Ortho Evra patch. The manufacturer, Ortho McNeil Pharmaceuticals is conducting additional studies to compare the risk of developing serious blood clots in women using Ortho Evra to the risk in women using typical birth control pills that contain 35 micrograms of estrogen.
The new labeling information is available along with additional information for healthcare providers and consumers online at: www.fda.gov/cder/drug/infopage/orthoevra/default.htm.
As I have stated elsewhere, I remain concerned at the standard practice adopted by the FDA in its approval processes whereby consumers are treated as little more than experimental subjects in the final testing stages of pharmaceuticals, all of which present some known dangers. The trouble is, the drugs also prove over time that they present many unknown dangers as well.
People place their trust in their prescribing doctors who in turn place their trust in what is in reality an unholy alliance between big pharma and the supposed regulators. Many times, I am happy to acknowledge, the FDA does act responsibly. This warning is a responsible thing to do for example. However, it is the fault of the whole system with which I take issue.
Most people are happy to remain ignorant and to be treated like guinea pigs or laboratory mice. Are you?
Increasingly these days there are alternative health services available to people. With substantial histories of demonstrated efficacy and well known safety profiles, selection from a vast array of alternative therapies and medicines certainly makes far more sense than taking the risks and putting up with the adverse reactions associated with prescribed drugs.
An Adverse Drug Reaction (ADR) is a negative side effect that occurs as the result of using a drug as prescribed. According to the New England Journal of Medicine ADRs affect 22 million people each year.
Many ADRs are not even reported however since they are not directly caused by the drug. Instead, they are triggered by drug-induced nutritional deficiencies. The FDA does not require drug companies to report whether or not an approved drug can provoke such a response, assuming they have even bothered to determine such a possibility.
As a result, most physicians and pharmacists are unaware of the magnitude of the problem. Indeed, it may possibly be the case that even the drug companies are not fully aware of the problem.
This lack of awareness among health professionals puts millions at risk for poor health and even premature death. Whilst many adverse drug reactions may not be especially severe, many certainly are. The most serious of course, is death, but it is difficult to assess how much life is lost in terms of unnecessary early deaths, as opposed to immediate or obvious deaths directly linked to an ADR.
By far the best approach is to strictly avoid all except the most essential drugs. I know many doctors who would claim they only ever prescribe necessary medication. But then, I know some politicians who claim they never lie.
The sad truth is that we cannot trust doctors not to prescribe dangerous drugs. It isn’t entirely their fault; the fact is all drugs are dangerous. So ultimately it comes down to you. Avoiding ADRs may be your call. Remember, it’s your life.
The recent increase in the use of testosterone therapy has led to concern over prostate cancer, known to be linked to high testosterone levels. A team of researchers from the University of California at San Diego Medical Center report on 20 cases of prostate cancer developing in men a few months to a few years after they began testosterone supplementation for sexual dysfunction or "rejuvenation". (See: Gaylis, F. D. et al. Prostate cancer in men using testosterone supplementation. The Journal of Urology, Vol. 174, August 2005, pp. 534-38.)
The average PSA (prostate-specific antigen) level of the 17 men tested before treatment was 3 nanograms per milliliter, although the range was 1 to 15. The threshold for further evaluation is usually 4. The researchers say that in these 20 patients, clinically significant prostate cancer was presumed to be related to testosterone therapy.
Although the authors state that there is no conclusive evidence yet, they add that in their opinion, men should not receive a prescription for testosterone supplementation without careful, informed consultation regarding the risks and benefits of such treatment. This is particularly relevant for those with a family history of prostate cancer.
Furthermore, the authors are concerned about the high prevalence of subclinical prostate cancer and how testosterone supplementation might affect such tumors. They hope that expert guidelines will be drawn up to aid doctors in appropriately and carefully prescribing testosterone replacement to men who need it, monitoring them for potential adverse outcomes.
The article appears alongside an editorial by a urologist from Cornell University who points out "serious flaws" in the study. For example, it does not show how common the risk of prostate cancer is in men on testosterone therapy. If results from a previous study are accurate, it may be no higher than in the general population. Moreover, in this study there is a lack of pre-treatment data for many of the patients on PSA or DRE (digital rectal examination). Nevertheless, doctors need to be extremely careful before beginning testosterone therapy, he writes, and PSA and DRE testing should be performed frequently during treatment.
The criticisms notwithstanding, it is interesting to note that, the FDA recently updated the Warnings, Precautions and Adverse Reactions sections of the literature related to AndroGel (testosterone gel) 1%. The changes are relevant and quite significant as you can see below.
WARNINGS
PRECAUTIONSCarcinogenesis, Mutagenesis, Impairment of Fertility – Human Data
Summary of Changes to Contraindications and Warnings
Increases in serum PSA from baseline values were seen in approximately 18% of individuals in an open label study of 162 hypogonadal men treated with AndroGel for up to 42 months. Most of these increases were seen within the first year of therapy.
Anyone who foolishly uses, or rather abuses, testosterone supplements for less than genuinely pressing clinical reasons should stop immediately and consult a doctor for a thorough examination. Regrettably, it has become fashionable for some to resort to testosterone hormone supplementation for entirely inappropriate reasons.
Are you still taking statins? You know the old saying: when lawyers make mistakes they go to prison, but when doctors make mistakes, they bury them! So here’s a thought: why not ask your doctor if he or she has complete confidence in the statins that have been prescribed for you (you’re not a self-medicating Britton I trust). When you get an affirmative reply just say, that’s great doc, now just put that in writing for my lawyer will you please, so if you’re wrong my family can sue you and the drug company.
Those extra complaints you may have had since starting statins have no doubt been good for your doctor’s income so it seems fair to name him or her in your suit. For instance, have you developed any signs of kidney disfunction? You may well have, whether your heart is any safer or not. You see, it could result from just one of the adverse side effects of cholesterol- lowering statin drugs. One of those side effects is muscle pain (have you had any of that?). In some patients, statin use causes muscle cells to break down, which releases a protein into the bloodstream that can impair kidney function and even lead to kidney failure.
Many published reports about statins describe muscle pain as a "rare" side effect. I must see a distorted sample of the population because I have encountered it many times. Actually, if you visit some online health forums you’ll quickly see that this side effect is certainly not rare. Here are just a few first-hand accounts.
One poster had muscle pains with a statin drug, and now wants to know, "Does the muscle pain ever go away? I have been off for about 1 week and it is a little better but still hurts."
Another posts: "Enough! Apart from the skin rash, the insomnia and twitching in bed, I had brand new muscle pains. It took about 5 or 6 weeks for those pains to fade. And about the same time for the rash to fade, too. Sleep normalized within a few days. Statins? Pure poison."
Another: "I had muscle pain while taking statins. After I stopped, the pain SLOWLY went away. Also my liver enzymes got elevated from taking them."
Another poster notes that: "Most people don’t realize that any muscle pain associated with statins is your body’s way of saying, Toxic! I let my doc talk me into statins a few years ago, tried 3 different ones and got slight muscle pains with each one."
There are countless posts about muscle pains and joint problems while taking statins. There are also reports of liver problems, which is not surprising, since the liver is the organ responsible for manufacturing your cholesterol. The overall exposure in the population to statin drugs is massive. Far from finding any comfort in that, I simply wonder at the enormity of the problem. And yes, I mean enormity (meaning, gross wickedness). It may take a few more years, but we’ll eventually see quite a big stink about statins I predict.
What makes it all the more tragic is that there are highly effective and perfectly safe ways of reducing harmful levels of cholesterol.
A new medication under review by the Food and Drug Administration (FDA) that may regulate blood glucose levels and have a beneficial effect on blood cholesterol and lipid levels for patients with Type 2 diabetes appears to increase the risk for major adverse cardiovascular events and death, according to a new study in JAMA released in late October (www.JAMA.com). Note that this was released via the website due to its importance to public health.
The medication, muraglitazar, is in a class of drugs called dual peroxisome proliferator-activated receptors (PPARs), that affect lipid levels and glycemic control in diabetic patients. The studies on muraglitazar were reviewed by an FDA advisory committee on September 9, 2005, resulting in a vote of 8 to 1 recommending approval for its use as a monotherapy in controlling blood glucose levels in patients with type 2 diabetes. On October 18, 2005, the FDA issued an "approvable letter" for muraglitazar, indicating that the drug could be approved once the FDA receives and reviews additional information.
Steven E. Nissen, M.D., and colleagues from the Cleveland Clinic Foundation, reviewed the FDA briefing documents made available via the FDA website for the September 9 public hearing. The researchers analyzed the muraglitazar trials performed in diabetic patients, publicly released by the sponsor and FDA for the advisory panel meeting. The documents provided data for five clinical trials that assessed safety and efficacy in diabetic patients.
The researchers restricted their analysis to treatment groups using muraglitazar doses of 5 mg/d or less. The analysis yielded 2,374 patients exposed to muraglitazar and 1,351 patients exposed to other agents, of which 823 received pioglitazone (an approved and currently available PPAR) and 529 placebo. The patients were relatively young (average age 55 years or less) and obese (average body mass index greater than 30). The studies included both men and women participants and the diabetes control among the participants was relatively poor.
The authors stated that "In the muraglitazar-treated patients, death, MI (heart attack), or stroke occurred in 35 of 2,374 (1.47 percent) patients compared with 9 of 1,351 (0.67 percent) patients in the combined placebo and pioglitazone treatment groups (controls)."
"The results of this analysis are concerning," the authors write. "For the most widely accepted composite end point of death, MI (heart attack), and stroke the RR (relative risk) for muraglitazar was 2.23. Other end points using narrower definitions (including only cardiovascular death) or broader composites (including CHF [congestive heart failure] and TIA [transient ischemic attack] events) showed similar risks." The reviewers note that the results are particularly concerning because the excess of adverse events was observed after the study participants had only limited drug exposure ranging from 24 to 104 weeks.
The researchers make the important points that:
- "atherosclerotic cardiovascular disease is particularly common in patients with type 2 diabetes, representing the cause of death in approximately 80 percent of diabetic patients. Thus, any drug used to treat diabetes requires careful scrutiny for its effects on atherosclerosis-related outcomes, such as MI and stroke." and
- "some important conclusions are warranted. Muraglitazar appears to increase the risk for morbidity and mortality in diabetic patients during relatively short-term treatment. The estimated magnitude of this risk is substantial with RRs indicating a doubling for irrevocable, major end points and composite outcomes. The consistency of these RRs suggests that this result is not due to chance. Accordingly, muraglitazar should not be used or approved to treat patients with diabetes until an appropriate dedicated trial to assess cardiovascular outcomes is performed".
This is an excellent case study for anyone wanting to examine the effectiveness of web based publishing in contributing to the dissemination of health related information. Such publishing may take place at many levels in order to ensure the widest possible community distribution. In this case, the information was of a professional and technical nature and the web facilitated critical evaluation and effective communication to both regulatory authorities, the medical profession and the interested wider public.
Let us hope that the critical review of the data effectively informs the approving authorities and that they make the only possible safe decision to not approve muraglitazar.