meridia

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http://www.healthsquare.com/newrx/mer1254.htm

Brand name:
Meridia
Pronounced: mer-ID-dee-uh
Generic name: Sibutramine hydrochloride




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Meridia helps the seriously overweight shed pounds and keep them off. It is especially recommended for those who in addition to being overweight have other health problems such as high blood pressure, diabetes, or high cholesterol. It is used in conjunction with a low-calorie diet.

Meridia works by boosting levels of certain chemical messengers in the nervous system, including serotonin, dopamine, and norepinephrine.


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Most important fact about this drug
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Make a point of keeping follow-up appointments with your doctor. Meridia can increase your blood pressure, so it's important to have your blood pressure and pulse monitored at the beginning of therapy and regularly thereafter.


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How should you take this medication?
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Meridia can be taken with or without food.

--If you miss a dose...

Take it as soon as you remember. If it is almost time for your next dose, skip the one you missed and go back to your regular schedule. Do not take 2 doses at once.

--Storage instructions...

Store at room temperature away from heat and moisture in a tight, light-resistant container.


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What side effects may occur?
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Side effects cannot be anticipated. If any develop or change in intensity, inform your doctor as soon as possible. Only your doctor can determine if it is safe for you to continue taking Meridia.


More common side effects may include:
Abdominal pain, acid indigestion, anxiety, back pain, constipation, cough increase, depression, dizziness, dry mouth, flu symptoms, headache, increased appetite, insomnia, joint pain, loss of appetite, loss of strength, nasal inflammation, nausea, nervousness, painful menstruation, rash, sinus inflammation, stomachache, sore throat


Less common side effects may include:
Acne, abnormal thinking, agitation, allergic reaction, arthritis, bronchitis, changes in taste, chest pain, dental problems, diarrhea, difficulty breathing, drowsiness, ear pain, ear problems, emotional changes, fever, gas, heavy uterine bleeding, herpes simplex virus, increased heart rate, increased blood pressure, itching, laryngitis, leg cramps, menstrual problems, migraine headache, muscle ache, neck pain, rectal problems, reduced vision, stimulation, stomach and intestinal inflammation, sweating, swelling, thirst, throbbing heartbeat, tingling skin sensation, urinary tract infection, vaginal yeast infection, vomiting


Rare side effects may include:
Bleeding problems, kidney problems, seizures




Why should this drug not be prescribed?
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If Meridia gives you an allergic reaction, you won't be able to use it. You should also avoid Meridia (and certainly don't need it) if you suffer from the compulsive dieting disorder known as anorexia nervosa. Do not combine Meridia with other drugs used to suppress appetite, and do not use it within 2 weeks of taking a drug classified as an MAO inhibitor, including the antidepressant medications Marplan, Nardil, and Parnate.


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Special warnings about this medication
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Use Meridia with caution if you have uncontrolled high blood pressure; it could make the problem worse. Avoid Meridia completely if you've had a stroke or suffer from heart disease, heart failure, or irregular heartbeat. Also avoid it if you have severe kidney or liver problems; the drug has not been tested under these conditions. Seizures are a rare, but possible, side effect. If you've had seizures in the past, use Meridia with caution. If you have a seizure while taking the drug, stop using it and call your doctor immediately.

Any drug that acts on the nervous system can theoretically impair judgment, thinking, and motor skills. Meridia does not seem to have this effect, but caution is still in order until you know how the drug affects you.

If you have narrow-angle glaucoma or thyroid problems, make sure the doctor knows; Meridia should be used with caution in these circumstances. If you are prone to gallstones, be aware that weight loss can cause more of them to form. Meridia has not been tested in people under 16 years old. It should be used with caution in those over 65. Although it has been classified as a controlled substance (potentially subject to abuse), the possibility of developing physical or psychological dependence is low.


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Possible food and drug interactions
when taking this medication
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Remember that Meridia must never be taken within 2 weeks of using an MAO inhibitor such as Marplan, Nardil, or Parnate. The combination could lead to serious, even fatal, overstimulation.

Meridia may also interact with a wide variety of other prescription and over-the-counter drugs, especially weight-reducing agents, decongestants, antidepressants, allergy medications, and cough and cold remedies that contain ephedrine or pseudoephedrine. Among the many drugs that pose a potential problem are the following:
Alcohol (excessive amounts)
Dextromethorphan (found in many over-the-counter cough preparations)
Dihydroergotamine (D.H.E. Injection, Migranal Nasal Spray)
Erythromycin (Eryc, Ery-Tab, PCE)
Fentanyl (Duragesic)
Fluoxetine (Prozac)
Fluvoxamine (Luvox)
Ketoconazole (Nizoral)
Lithium (Eskalith, Lithobid)
Meperidine (Demerol)
Naratriptan (Amerge)
Paroxetine (Paxil)
Pentazocine (Talwin NX, Talacen)
Sertraline (Zoloft)
Stimulants such as amphetamines, Dexedrine, Desoxyn, Adderall, Didrex, and Ionamin
Sumatriptan (Imitrex)
Tryptophan (L-Tryptophan)
Venlafaxine (Effexor)
Zolmitriptan (Zomig)

If you have any doubt about the safety of a combination, be sure to check with your doctor.


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Special information
if you are pregnant or breastfeeding
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The use of Meridia during pregnancy is not recommended. If you are in your child-bearing years, take reliable contraceptive measures while using this drug. If you do become pregnant, or plan on becoming pregnant, tell your doctor immediately. It is not known whether Meridia appears in breast milk; its use while breastfeeding is not recommended.


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Recommended dosage
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ADULTS


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The starting dose is 10 milligrams once daily. If you have not lost at least 4 pounds after 4 weeks, the doctor may increase the dose to 15 milligrams daily. This is the maximum; if weight loss still fails to appear, Meridia will be discontinued.

For those who experience side effects at the 10-milligram level, a 5-milligram dose may prove sufficient.

Use of Meridia for longer than 1 year has not been studied.


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Overdosage
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Although doctors have had little experience with overdoses of Meridia, increased heart rate and blood pressure are possible results. Since any medication taken in excess can have serious consequences, seek medical attention immediately if you suspect an overdose.

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http://www.vanderbilt.edu/AnS/psycho...gy/Meridia.htm

Meridia: The New Anti- Obesity Drug

Anjali Shah

Introduction
In today’s society the hegemonic belief surrounding weight is that thin is in and fat is out. With over half of the American population being overweight, the diet craze has swept the nation. However, a bigger player has come into the weight loss scene, the pharmaceutical industry. After the abrupt withdrawal of two anti- obesity drugs from the market in 1997, the pharmaceutical industry has been looking to fill the void in this area of the market. Meridia (sibutramine hydrochloric monohydrate), manufactured by Knoll Pharmaceutical Co, enters with caution what now appears to be a virtually deserted and uncertain anti- obesity market. The drug works to suppress appetite via serotonin (and norepinephrine) re-uptake inhibition.

How Does Meridia Work?
In the fall of 1997, fenfluramine (the fen half of the popular fen-phen drug combination) and Redux (dexfenfluramine) were recalled after the drugs were linked to potentially fatal heart valve abnormalities. In November of 1997, only a few months after the withdrawal of fenfluramine and Redux, the Federal Drug Administration (FDA) approved Meridia. Meridia is a class of drug known as monoamine (serotonin and norepinephrine) re-uptake inhibitors. It falls in the same class of many anti- depressants such as Prozac. Serotonin is a chemical released in the brain after you have eaten a meal, which makes you feel full. When a nerve impulse reaches the end of the nerve (the nerve terminal), the impulse causes the release of chemicals called neurotransmitters. The neurotransmitters are released in the space between the two adjacent neurons, this region is called the synaptic cleft. Usually once the neurotransmitters have bound to their receptors (the neurotransmitter and the receptor fit like a lock and a key) on the adjacent nerve, transport proteins work to reabsorb the extra neurotransmitter back into the nerve terminal so that they can be reused. However, Meridia acts to inhibit the reabsorption of serotonin so the that signal lasts longer, thus giving the sensation that you are full for a longer period of time. This method is thought to effectively reduce the caloric intake of an obese individual due to appetite suppression. For an informational video on the mechanism of action for Meridia visit the world wide web at www.4meridia.com/hcprof/fma.htm.

How is Meridia Different from the Recalled Drugs?
Although Meridia and fenfluramine have similar mechanisms of action (they both affect serotonin), fenfluramine boosts the levels of serotonin into the blood stream. This increase in the levels of serotonin is believed to have caused the heart valve damage seen in some patients. Essentially the difference between the two drugs is that Meridia is more localized, whereas fenfluramine has a systemic effect. Because of this difference, researchers believe that Meridia will not be linked with heart valve damage. As stated by Lawrence Cheskin, M.D., director of the Johns Hopkins Weight Management Center in Baltimore, "Meridia bypasses the heart and acts directly on the brain’s appetite control center. Meridia maintains serotonin levels in the brain, thereby curbing some carbohydrate cravings (Brietzke, 90)". Carbohydrates boost levels of serotonin in the brain, and this impacts appetite and mood so when your brain is running low on the chemical, it tells you to refuel. Meridia keeps serotonin levels elevated, short-circuiting these mentally fueled cravings. The drug also boosts adrenaline levels, curbing overall appetite.

Side Effects
Though Meridia may be safer than other anti- obesity drugs, it still warrants caution. The most troubling side effects include increase in blood pressure, heart rate, and abnormal heart rhythms (arrythmias) seen in some participants during clinical trials. However, most of these side effects were observed in participants who took large doses (more than 15 mg) of the drug (Portyansky, 23). Blood pressure elevations were controlled in these trials with dose adjustments . Those who do have high blood pressure to begin with are urged to weigh the benefits and risks of taking this drug. Meridia’s labeling recommendations calls for blood pressure and pulse measurements prior to therapy initiation and regular monitoring thereafter for all patients. For more information on the increase in blood pressure and heart rate go to www.4meridia.com/hcprof/fsa.htm on the world wide web. The most commonly reported side effects include dry mouth, headache, constipation, and insomnia, "but people seem to find these effects pretty tolerable", according to Cornell Medical Center’s Dr. Louis Aronne (Anonymous, 98).

Who Should Take Meridia?
Meridia is targeted for the seriously obese and not for those who are looking to lose a few pounds. Linda Mayer, director of communications at Knoll, states, "This is serious medicine, and it is only for certain people. In the past, there has been too much emphasis on cosmetic use of obesity drugs. We’re focusing on the health benefits. It is not about how you look but instead about how your health will improve if you lose weight (Fentress, 33-34)". This drug is recommended only for obese patients with an initial body mass index (BMI) greater or equal to 30 ( a person who is 5’5" and weight 180 pounds), or a BMI of 27 in the presence of other risk factors, such as diabetes, hypertension, arthritis, sleep apnea, or dyslipidemia (low HDL and high triglycerides) (Fentress, 33-34). BMI is a measurement based on height and weight as they relate to body fat. It can be used to determine how much risk people have of developing certain health problems because of their weight. Someone with a BMI of 27 is approximately 20% overweight. The higher the BMI, the greater the risk a person has to develop additional health problems. To calculate your BMI you can go to www.4meridia.com/consumer/archive/bmi.cfm.
Knoll’s web site (www.4meridia.com/consumer/3200.html#5) states that the drug should not be used by patients who:
· take drugs called monoamine oxidase inhibitors (MAOI’s), which are used for depression, Parkinson’s Disease, and other disorders. This is very important because serious, sometimes even fatal, reactions can occur if Meridia is taken at the same time MAOI’s are taken;
· take other weight loss medicines that act on the brain, such as phentermine. This includes prescription drugs, over- the- counter medicines, and herbal products;
· are allergic to sibutramine;
· have coronary heart disease, angina (heart related chest pain), arrythmias, prior heart attack or congestive heart failure;
· have severe kidney or liver disease;
· have had a stroke or symptoms of a stroke;
· are pregnant, planning to become pregnant, or breast- feeding;
· suffer from anorexia nervosa;
· take drugs for depression; have had seizures;
· have an eye disorder called narrow angle glaucoma;
· are under 16 years of age;
· take other drugs that regulate serotonin. Combining Meridia with other serotonin regulators can cause a rare, but serious condition called "serotonin syndrome", which requires immediate medical attention and may include symptoms such as restlessness, loss of consciousness, confusion, disorientation, tremors, and increased heart rate. Other serotonin regulators include most anti- depressants, , some migraine headache therapies, lithium, tryptophan, and dextromethorphan (cough suppressant).
A gray area exists between people who should get Meridia, and those who should not. While recommended for people with cardiovascular risk factors (due to obesity), those who have crossed the line into disease are excluded (Chase, B1). But how do you exclude people with undiagnosed heart disease? According to Dr. Michael Schwartz, an obesity researcher at the University of Washington, Seattle, "At minimum, careful history and a physical exam are required to pinpoint unacceptable risk. For some a treadmill test could help", he further states, "Among the obese with high cholesterol and hypertension, a certain percentage will have coronary heart disease and not know it. In such people, a drug which raises blood pressure and pulse could trigger angina, so anyone who experiences chest pain on Meridia should be advised to stop the drug (Chase, B1)". It seems slightly ironic because people who have hypertension and high blood pressure (due to obesity) are the ones who are most likely to want the drug, yet these are the people who are urged not to take it.

The Effectiveness of Meridia
And now the million dollar question, "how much weight can you lose"? In the Knoll clinical studies, overweight patients on Meridia and a reduced calorie diet, in combination with lifestyle modifications, achieved an average of 5 to 10 percent weight reduction from their initial weight at various dosage levels. In one 12 month study, patients who took 10 mg of Meridia daily lost an average of 10 pounds, while those taking 15 mg daily lost an average of 14 pounds. The average weight loss in people on only a reduced calorie diet was 3.5 pounds. Study participants lost most of their weight in the first six months and maintained statistically significant weight losses for up to a year (Fentress, 33-34). Although Meridia’s efficacy profile is modest, the drug’s sustained actions are advantageous since obesity tends to be a chronic condition. Timothy Seaton, M.D., senior medical director at Knoll claims, "the maintained amount of weight loss is enough to reduce obesity- related health risks, including diabetes, osteoarthritis, hypertension and certain types of cancer (Portyansky, 23)".
For those who are trying to lose weight, it is often difficult to stay focused on lifestyle changes and motivated to exercise when all they can think about is food. Knoll claims that Meridia is designed to solve that problem. "Meridia helps patients comply better with an improved lifestyle", said Mayer (director of communications at Knoll), "one patient I spoke with said it felt like she had eaten a bag of popcorn, so she wasn’t so hungry that all she could do was think about food". Mayer warns, "It is important for people to have realistic expectations, Meridia should be used as part of a comprehensive lifestyle management program" (Fentress, 33-34). While Meridia takes your mind of food, Knoll is stressing that it is not likely to be a magic bullet for weight problems.

Clinical Studies
In a randomized, placebo controlled, double blind study done in Denmark , the group evaluated the effect of sibutramine on energy expenditure and appetite during chronic (8 weeks) treatment without dietary restriction on 32 (seven male, 25 female) healthy obese patients with a BMI of about 34. The results show that sibutramine does cause a significant weight loss as compared to the placebo (2.4 kg vs. 0.3 kg). The 24 hour energy expenditure also decreased significantly less in the treated group, as well as significantly decreased hunger and anticipated food consumption, and increased satiety scores. The study concluded that the weight reducing effect of sibutramine is caused by a dual mechanism: reduction of energy (calorie) intake by increasing satiety and decreasing hunger and prevention of the decline in energy expenditure that follows weight loss (Hansen et al, 1016-24).
In another study 19 obese female patients receives sibutramine treatment for 12 weeks while the control group received a placebo, both groups were offered dietary advice. This study tested the hypothesis that an increase in energy expenditure contributes to weight loss, and the effects of sibutramine on heart rate and cardiac output were also assessed. The results showed that those on the sibutramine treatment reduced their weight by about 8.1 % in 12 weeks as opposed to the placebo group who reduced their weight by about 5.1%, and there were no significant cardiovascular changes between the two groups. The group concluded that the increase in energy expenditure is associated with weight loss, and this could allow greater numbers of people to maintain a greater degree of weight loss (Walsh et al, 1009-15).
A study conducted, at the University of Colorado Health Sciences Center in Denver assessed the effects of sibutramine on metabolism and weight loss in overweight women. Forty- four overweight women were randomized given either a placebo or sibutramine for eight weeks and both groups were restricted to a 1200 calorie a day diet. Sibutramine did reduce body weight as compared to the placebo group, however there was no change in the metabolic rate between the two groups. Another finding was that after the patients were taken off medication, they were able to keep their weight stable for another 4 weeks (Seagle et al, 115-21).
In a study done by a Knoll Pharmaceuticals lab in France, the group tested the efficacy and tolerability of sibutramine in obese patients in a multi- center, double- blind, and placebo- controlled study. 235 subjects, aged 18-65 and a BMI within the range of 27-40 were randomized to receive placebo or sibutramine treatment over a 12 week period, advice on diet and behavior modification was provided. The group mean weight loss at the end of the study for the treated group was 2.4 kg for the 5 mg/day dose, 5.1 kg for 10 mg/day dose, and 4.9 kg for 15 mg/day dose. The incidence and type of adverse events and the rate of withdrawal, were not significantly different in the four groups. No changes in blood pressure were found, but a significant increase in heart rate (4 beats/min) was found in patients who received 10 mg or 15 mg sibutramine compared with placebo Hanotin et al, 32-8).
Also another study conducted in conjunction with a Knoll scientist (Dr. Timothy Seaton, medical director at Knoll) found "Small mean increases in blood pressure and pulse rate (with considerable individual variability) were observed in patients treated with sibutramine. Most of the adverse events observed on sibutramine are related to its pharmacology, including small mean increases in blood pressure and heart rate" (Bray et al, 189-98). These studies may slightly down play the increase in blood pressure and heart rate finding because these studies were associated with Knoll pharmaceuticals. However, Knoll does acknowledge this problem and addresses it through dosage adjustments.
In a clinical trial in France, a group conducted a 1 year treatment with sibutramine (10 mg) or placebo on patients who had a BMI greater than 30. These patients were also put on a very low calorie diet. This study also found a significant increase in weight loss, with 86% of the sibutramine patients losing at least 5% of their weight compared to 55% of those in the placebo group. Similarly, at month 12, 75% of subjects in the sibutramine group maintained at least 100% of the weight loss achieved with a very low calorie diet, compared with 42% in the placebo group. The group concluded that following a very low calorie diet, sibutramine is effective in maintaining and improving weight loss for up to a year Apfelbaum et al, 179-84).

Conclusion
After reviewing these studies and evaluating the claims set forth by Knoll Pharmaceuticals, it seems that Meridia is a sufficient tool for weight loss. The amount of weight loss that one can expect is about 5 to 10 percent weight reduction from their initial weight at various dosage levels (5, 10, and 15 mg), however, 10 mg is the most common dosage prescribed. Though this drug is effective there are some dangerous side effects including elevated blood pressure, increased heart rate and prevalence of arrythmias. Robert H. Eckel, M.D., vice chairperson of the American Heart Association’s Nutrition Committee and professor of medicine at the University of Colorado Health Sciences Center states, "Before definitive data are available, patients and their physicians should carefully weigh the benefits vs. the risks of using this new medication. It is especially important that this drug be considered only for people for whom obesity poses a health risk"(http://www.americanheart.org/Whats_N...es/974832.html). Also, this drug is not expected to cause heart valve damage as was observed in previous anti- obesity drugs. But it is best to be cautious about Meridia because no long term studies have been done, a least not beyond a year. Once again, this drug is for the purposes of treating obesity, therefore only people with a BMI of 30 (or 27 in the presence of other risk factors) should be taking this drug. The primary goal of this drug is not necessarily to make you look better, but to help you lose enough weight to eliminate health risks associated with obesity. People taking Meridia or considering it should also be reminded that Meridia must be used in conjunction with major lifestyle changes, such as increasing physical activity and eating right. Those who have a BMI under 30 with no risk factors are encouraged to maintain a healthy lifestyle.




References

Apfelbaum, M., Vague, P., Ziegler, O., Hanotin, C., Thomas, F., Jones, SP., Leutenegger, (1999). Long- term maintenance of weight loss after a very- low calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine. American Journal of Medicine, Feb; 106(2): 179-84.

Bray, GA., blackburn, GL., Ferguson, JM., Greenway, FL., Jain, AK., Mendel, CM., Mendels, J., Ryan, DH., Schwartz, SL., Scheinbaum, ML., Seaton, TB. (1999). Sibutramine produces dose- related weight loss. Obesity Research, Mar; 7(2): 189-98.

Brietzke, Carol. (1998). Phen- Fen all over again?. Cosmopolitan, August: 90.

Chase, Marilyn. (1998). A New Diet Drug Hits the Marketplace, With Potential Risks. Wall Street Journal, March 2: B1.

Fentress, Debbie. (1998). New anti- obesity drug comes to market. Diabetes Forecast, June; 51(6):33-34.

Hanotin, C., Thomas, F., Jones, SP., Leutenegger, E., Drouin, P. (1998). Efficacy and Tolerability of Sibutramine in Obese Patients: A Dose- Ranging Study. International Journal of Obesity Related Metabolism Disorders, Jan; 22(1): 32-8.

Hansen, DL., Toubro, S., Stock, MJ., Macdonald, IA., Astrup, A. (1999). The effect of sibutramine on energy expenditure and appetite during chronic treatment without dietary restriction. International Journal of Obesity Related Metabolism Disorders, Oct; 23(10): 1016- 24.

Portyansky, Elena. (1998). A near empty diet market welcomes new anti- obesity drug. Drug topics, Jan; 142(1): 23.

Seagle, HM., Bessesen DH., Hill, JO. (1998). Effects of sibutramine on resting metabolic rate and weight loss in overweight women. Obesity Reseach, Mar;6(2):115-21.

Walsh, KM., Leen, E., Lean, ME. (1999). The effect of sibutramine on resting energy expenditure and adrenaline- induced thermogenesis in obese females. International Journal of Obesity Related Metabolism Disorders, Oct;23(10):1009-15.

Anonymous. (1998). Beyond Phen- Fen: Are the new diet pills for you? Woman's Day, May 12, 61(9): 98.

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Journal of Family Practice, Dec 2001 v50 i12 p1084(1)
Does long-term use of sibutramine (Meridia) result in continued weight loss in short-term responders? (POEMs). J. Herbert Stevenson; Thomas Trojian; Eric A. Jackson.
Full Text: COPYRIGHT 2001 Appleton & Lange

Wirth A, Krause J. Long-term weight loss with sibutramine: a randomized controlled trial. JAMA 2001; 286:1331-39.

* BACKGROUND Obesity, defined as a body mass index (BMI) equal to or greater than 30 kg/[m.sup.2], is a common chronic disorder with a prevalence of 22.3% in American adults. (1) There is significant interest in pharmacologic interventions for this disorder because of the difficulty achieving and maintaining significant weight loss solely with lifestyle changes. Two drugs, sibutramine and orlistat (Xenical), have recently been approved by the Food and Drug Administration for long-term (greater than 12 weeks) management of obesity.

* POPULATION STUDIED The researchers enrolled 1102 obese (BMI = 3040 kg/[m.sup.2] adults from 111 private practices or outpatient clinics in Germany. Almost all subjects were white, and 75% were women aged between 18 and 65 years. After randomization, treatment groups were well matched demographically and had similar weights, BMI (mean = 34.8 kg/[m.sup.2], and waist circumference. Patients were excluded if they were pregnant or had serious cardiovascular or metabolic diseases, history of drug or alcohol abuse, depression, or treatment with antidepressants, [Beta]-blockers, or any drug influencing body weight.

* STUDY DESIGN AND VALIDITY This was a randomized (allocation assignment concealed) double-blind trial funded by the manufacturer of sibutramine. All patients were treated unblinded with 15 mg per day of sibutramine for 4 weeks. Patients with at least a 2% or 2 kg weight loss (responders) were then randomized to 1 of 3 treatment groups: 15 mg per day of sibutramine continuously during weeks 5 to 48; 15 mg per day of sibutramine intermittently during weeks 5 to 12, 19 to 30, and 37 to 48 and a placebo on all other days; or placebo once daily for weeks 5 to 48.

To mimic routine ambulatory practice in Germany, the study did not include formal dietary or behavior modification programs. Unfortunately, the use of potentially confounding variables, such as diet or exercise, were not reported. Differences in diet or levels of exercise between the 3 study groups could have had a significant impact on study results. Also, there was no testing of whether the side effects or weight loss produced by the medication allowed participants to identify the treatment group to which they were assigned. Correct identification of treatment group assignment by participants would suggest unsuccessful blinding, threatening the validity of study results. The results of this trial are only applicable to relatively healthy white persons.

* OUTCOMES MEASURED The primary outcome was weight loss during the 44-week randomized period. Secondary outcomes included waist circumference, heart rate, blood pressure, cholesterol levels, and side effects.

* RESULTS The average weight loss for the 1001 patients completing the 4-week nonblinded run-in period was 4.2 kg and was similar for patients going into each of the 3 treatment groups. Using intention-to-treat analysis, sustained mean weight loss during the 44-week randomized treatment period was 3.8 kg (4.0%) with continuous sibutramine therapy (95% confidence interval [CI], -4.42 to -3.20 kg) and 3.3 kg (3.5%) with intermittent therapy (95% CI, -3.96 to -2.66 kg). Mean weight gain in the placebo group was 0.2 kg (95% CI, -0.60 to 0.94 kg). Minimal decreases in low-density lipoprotein cholesterol (-5 mg/dL) occurred in both sibutramine treatment groups, but blood pressure was not affected. During the 4-week run-in period where everyone received sibutramine, 14% of the patients experienced drug-related adverse effects. During the 44-week double-blinded period, the proportion of withdrawals because of adverse events was similar across the 3 study groups. Twenty-one percent of the original subjects did not complete the entire 48-week study.

RECOMMENDATIONS FOR CLINICAL PRACTICE

Sibutramine 15 mg per day given continuously or intermittently for 44 weeks allows modest additional weight loss (3.55 kg, 7.8 lb) compared with placebo among initial sibutramine responders. This weight loss was achieved in a group of obese (mean BMI = 34.8 kg/[m.sup.2]), otherwise healthy women, most of whom were white. The same results may not occur in other races, and may not be applicable to many practices. Because truly long-term (beyond 1 year) safety, health, or mortality benefits have not been established for sibutramine, this drug should not be routinely used for treating obesity.

REFERENCE

(1.) Kuczmarski RJ, Carrol MD, Flegal KM, Troiano RP. Varying body mass index cut-off points to describe overweight prevalence among U.S. adults: NHANES III (1988 to 1994). Obesity Res 1997; 5:542-48.

J. Herbert Stevenson, MD
Thomas Trojian, MD, MS
Eric A. Jackson, PharmD
University of Connecticut School of Medicine
and Saint Francis Hospital and
Medical Center Hartford
E-mail: ejackson2@stfranciscare.org

Products: Meridia (Medication) - Evaluation

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United Press International, Sept 12, 2003 p1008254w7962
Diet drug Meridia under fire again.
Full Text: COPYRIGHT 2003 United Press International

WASHINGTON, Sep 11, 2003 (United Press International via COMTEX)

The diet drug Meridia is under attack again by the consumer watchdog organization Public Citizen but the government says it will not change its position -- and physicians agree -- that the medication has a limited role to play in weight control.

Public Citizen has urged the Food and Drug Administration for some time to ban the prescription drug after discovering an increase in cardiovascular-related deaths and fetal abnormalities among young people who took Meridia.

In its second petition to FDA, Public Citizen urged the federal agency to take Meridia, known chemically as sibutramine, off the market and cited FDA's own data that linked the drug to serious side effects, including heightened blood pressure and heart attack -- as well as to 30 recent deaths.

"The reactions are serious, the number of victims is rising rapidly and the effectiveness in treating obesity is meager," Dr. Sidney Wolfe, director of Public Citizen's Health Research Group, said in the petition. "The FDA is in possession of evidence sufficiently clear to immediately ban this serious health hazard, known to cause dangerous increases in blood pressure."

Public Citizen found since its initial petition in March 2002, another 30 cardiovascular deaths among Meridia users were reported to the FDA, bringing the total to 49. Gleaning from the FDA's adverse event data, Public Citizen said 68 percent of the people who died were under age 50 and two deaths had occurred among women ages 28 and 30. There also were 124 cardiovascular side effects among Meridia users serious enough to warrant hospitalization.

New evidence also showed, Public Citizen argued, pregnant women who take Meridia could place their unborn children at risk for fetal abnormalities, such as congenital malformations of the heart and central nervous system. Miscarriage and stillbirth also have been linked to the drug, petition asserted. The group cited four babies born with heart defects connected to Meridia use and claimed the babies' conditions are consistent with findings seen in animal studies conducted prior to the drug's FDA approval.

Wolfe said this evidence illustrates the FDA lacks "justification in continuing to market a drug that provides minimal weight reduction while increasing the likelihood of injury and death."

In response, Abbott Laboratories of Abbott Park, Ill., the manufacturer of Meridia, sent United Press International a statement: "Sidney Wolfe's supplement to the March 19, 2002, Citizen's Petition to the FDA reflects a pattern of irresponsible conduct by Public Citizen. The safety of Meridia has recently been comprehensively re-examined by regulatory authorities, including the European Committee for Proprietary Medicinal Products and Canadian Health authorities, and they have concluded that the risk/benefit profile of Meridia remains favorable," the statement said.

"Meridia has been approved for use in treating obesity since 1997 and has been studied in more than 100 clinical trials involving 12,000 patients," it continued. "An estimated 12 million people in 75 countries have used Meridia for management of obesity."

Studies filed with the FDA show patients taking Meridia had moderate weight loss results, depending on the dosage. One study of patients taking the drug for 12 months, along with a low-calorie diet, found an average loss of 10 pounds, while another study found after six months the average weight loss was 21 pounds. Patients using Meridia also were better able to keep the weight off long-term, the studies concluded.

An FDA spokeswoman said Meridia would not be pulled from the market, nor would the agency order a label change.

"The agency, at this point in time, believes the labeling is sufficient and the drug is safe and effective if used according to the labeling," the spokeswoman told UPI. "We have been updating our adverse events report survey for Meridia. We've been examining the deaths related to cardiac disease."

When asked if Meridia posed any greater threat to patients compared to the other prescription diet drugs currently on the market, such as the popular Xenical, the FDA spokeswoman said, "We found no alarming difference in the reporting rates in cardiovascular deaths between Meridia and Xenical."

Xenical, known chemically as orlistat, works differently than Meridia. While Meridia suppresses appetite, Xenical blocks fat absorption. Side effects linked to Xenical are primarily gastrointestinal problems, such as leaky stools, but it has not been linked to severe cardiovascular problems. Some studies even suggest Xenical might help improve cholesterol. The drug is made by Hoffmann-La Roche Inc., in Nutley, N.J.

Studies that have looked at Meridia have found an association to cardiovascular problems. One study, conducted by researchers in Poland and published in the December 2002 issue of the International Journal of Obesity and Related Metabolic Disorders, found a dose-dependent relationship tied to increased blood pressure. The researchers noted, however, the drug's cardiovascular effects are related to the weight loss achieved and it does not seem to exacerbate pre-existing and controlled hypertension.

"I'm not aware of any substantial toxicity (of Meridia)," Dr. Robert H. Eckel, a spokesman for the American Heart Association and chairman of its council on nutrition, physical activity and metabolism, and a practicing endocrinologist in Denver. "The drug is modestly effective."

Eckel said the drug might increase the risk of heart palpitations and "needs to be used with more supervision or caution," but this doesn't mean the drug needs to be yanked from the market.

"Meridia has a place in the treatment of obesity, but that place is limited," he told UPI.

Obesity is a major public health epidemic in the United States. The latest Surgeon General's findings show nearly two-thirds or 61 percent of the entire American population is either overweight or obese -- children included.

"I don't think we should lightly toss (Meridia) the drug away," Dr. Howard Eisenson, director of the Duke Diet and Fitness Center at Duke University in Durham, N.C., told UPI.

"They've never been happy with it," Eisenson said of Public Citizen, "and the FDA has certainly reviewed a lot of evidence to come to their decision. I rely on the FDA to do a good job scrutinizing drugs for safety. Critics of the drug often say it's not helpful, but actually research suggests it's moderately helpful. The people on the drug do lose weight and keep it off longer than people who don't take the drug."

Dr. Keith Ayoob, a spokesman for the American Dietetic Association and an associate professor at Albert Einstein Medical School in New York City, said though Meridia might serve as a springboard to weight loss, it is a short-term solution to a complex problem.

"It's not a magic bullet and at some point you have to get off it," Ayoob told UPI. "Meridia, I know, has undergone a lot of review, but nothing is perfect. My concern about Meridia is the same it would be with any other clinical pill like Xenical or any other pill: It's a temporary solution."

The growing girth of the country has made diet pills a hot commodity and Meridia and Xenical top a relatively short list of FDA-approved prescription medications designed specifically for the treatment of obesity.

Concern over prescription weight loss medications was heightened in 1997 when FDA removed fenfluramine and dexfenfluramine -- the so-called fen-phen -- from the marketplace because of heart valve problems in patients taking the drugs, which are closely related chemically.

More and more physicians were prescribing the drugs -- which were first approved to be prescribed separately -- together in an off-label treatment.

By KATRINA WOZNICKI, UPI Science News

Copyright 2003 by United Press International.

News Provided by COMTEX (http://www.comtexnews.com)

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Consumer Reports, Dec 2003 v68 i12 p57(1)
Weight-loss drug fattens heart risks. (CR health)(Meridia)
Full Text: COPYRIGHT 2003 Consumers Union of the United States, Inc.

Is the diet drug sibutramine (Meridia) too dangerous to stay on the market? The Health Research Group at Public Citizen, a Washington-based consumer-advocacy organization, says it is, citing adverse events reported to the Food and Drug Administration.

From the drug's introduction in February 1998 through March of this year, the FDA received reports of 49 deaths from cardiac arrest, heart attack, and heart arrhythmia in people who were taking sibutramine. Another 124 people developed cardiovascular conditions severe enough to require hospitalization. The manufacturer, Abbott Laboratories, declined to tell us how many people are taking the drug.

"We would like nothing better than to see an effective weight-loss drug, but Meridia is not it," says Larry D. Sasich, Pharm.D., M.P.H., a researcher at Public Citizen. Obese people already are at risk for high blood pressure and heart problems. "So, the very people who would benefit most from weight loss face substantial risk from this drug," says Sasich.

Sibutramine encourages weight loss in part by stimulating the sympathetic nervous system, which boosts heart rate and blood pressure. The mechanism is similar to that of amphetamines, as well as nutritional supplements containing ephedra, which have also been linked to cardiovascular problems.

A spokesman for Abbott says that several studies on obesity show significantly higher death rates than the fatalities that occurred with the use of Meridia. "That tells us this is not related to drugs, but rather to the underlying disease that these patients have," says ]ames Embrescia, D.O., who monitors product safety for Abbott.

In clinical trials, severely overweight people who used sibutramine fo