About all

Topiramate and weight loss: The effect of topiramate on weight loss in patients with type 2 diabetes

Содержание

Phentermine and Topiramate: MedlinePlus Drug Information

Phentermine and topiramate come as extended-release capsules to take by mouth. The medication is usually taken with or without food once a day in the morning. This medication may cause difficulty falling asleep or staying asleep if it is taken in the evening. Take phentermine and topiramate at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take phentermine and topiramate exactly as directed.

Your doctor will probably start you on a low dose of phentermine and topiramate and increase your dose after 14 days. After you take this dose for 12 weeks, your doctor will check to see how much weight you have lost. If you have not lost a certain amount of weight, your doctor may tell you to stop taking phentermine and topiramate or may increase your dose and then increase it again after 14 days. After you take the new dose for 12 weeks, your doctor will check to see how much weight you have lost. If you have not lost a certain amount of weight, it is not likely that you will benefit from taking phentermine and topiramate, so your doctor will probably tell you to stop taking the medication.

Phentermine and topiramate may be habit forming. Do not take a larger dose, take it more often, or take it for a longer period of time than prescribed by your doctor.

Phentermine and topiramate will help control your weight only as long as you continue to take the medication. Do not stop taking phentermine and topiramate without talking to your doctor. If you suddenly stop taking phentermine and topiramate, you may experience seizures. Your doctor will tell you how to decrease your dose gradually.

Phentermine and topiramate is not available at retail pharmacies. This medication is available only through specific mail order pharmacies. Ask your doctor if you have any questions about how you will receive your medication.

Your doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with phentermine and topiramate and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer’s website to obtain the Medication Guide.

Phentermine/topiramate combo wins FDA approval for weight loss




ADD TOPIC TO EMAIL ALERTS


Receive an email when new articles are posted on

Please provide your email address to receive an email when new articles are posted on .


Subscribe

We were unable to process your request. Please try again later. If you continue to have this issue please contact [email protected] com.

Back to Healio

The FDA has approved extended-release phentermine plus topiramate as an addition to a reduced-calorie diet and exercise for chronic weight management in overweight or obese adults. The agency’s decision represents only the second approval of a weight-loss drug in more than a decade.

The drug, to be marketed as Qsymia (Vivus) is a combination of phentermine (Adipex, Gate), a sympathomimetic amine anorectic, and extended-release topiramate (Topamax, Janssen), an antiepileptic drug. The FDA has approved it for use in adults with an initial BMI of at least 30 or in those with a BMI of 27 or greater and at least one weight-related condition, such as hypertension, type 2 diabetes or dyslipidemia, according to a press release from the agency.

The recommended daily dose contains 7.5 mg of phentermine and 46 mg of extended-release topiramate. The drug will also be available at a higher dose, 15 mg of phentermine and 92 mg of topiramate, for select patients.

The approval of extended-release phentermine/topiramate follows the approval of another weight-loss drug, lorcaserin (Belviq, Arena Pharmaceuticals), with identical indications in June.

“Obesity threatens the overall well-being of patients and is a major public health concern,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a press release. “Qsymia, used responsibly in combination with a healthy lifestyle that includes a reduced-calorie diet and exercise, provides another treatment option for chronic weight management in Americans who are obese or are overweight and have at least one weight-related comorbid condition.”

Advisory panel decisions

In July 2010, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee recommended against approval of extended-release phentermine/topiramate, then referred to as Qnexa, and issued a complete response letter in October 2010. Although the drug met the two efficacy benchmarks, the agency said, the adverse effects associated with the drug, particularly psychiatric and cognitive events, teratogenicity, metabolic acidosis and cardiovascular events required further study.

During the July 2010 advisory committee meeting, panel member Elaine H. Morrato, DrPH, MPH, assistant professor in the department of health systems, management and policy at the University of Colorado, Denver, expressed apprehension about the drug’s approval.

“While I agree there is a significant obesity epidemic in the United States … my concerns were the public health consequences, given the long list of safety risks and the strong pent-up market demand,” Morrato said. “The drug will be used by millions of patients over long periods of time far exceeding the label indications for use and duration of clinical experience that we have.”

However, in February, the same advisory committee recommended approval of extended-release phentermine/topiramate, with the suggestion that the manufacturer conduct a postmarket, cardiovascular outcomes trial.

“The sponsor has done a good job at demonstrating efficacy, and they need to step up to the plate and do the cardiovascular outcomes trial and do it fast,” committee member Sanjay Kaul, MD, said during the second meeting. “There is opportunity for the sponsor to fully characterize the impact of the drug on heart rate and blood pressure.”

Evidence base

The safety and efficacy of extended-release phentermine/topiramate were evaluated in two randomized, placebo-controlled trials including 3,700 obese and overweight patients, with or without significant weight-related conditions. The patients received lifestyle modification consisting of a reduced calorie diet and regular physical activity.

Results from the trials showed that after 1 year of treatment with the recommended dose (7.5 mg phentermine, 46 mg of topiramate), patients experienced an average weight loss of 6.7%, and those who were treated with the highest daily dose (15 mg phentermine, 92 mg topiramate) had an average weight loss of 8. 9%. Sixty-two percent of patients lost at least 5% of their body weight with the recommended dose and 69% lost at least 5% with the highest dose, compared with approximately 20% of patients treated with placebo.

Moving forward

The approval comes with a warning for patients and clinicians under the Risk Evaluation and Mitigation Strategy (REMS), consisting of a medication guide designed to educate patients and clinicians about the important safety information to assure it is prescribed and taken properly. Moreover, the drug will only be dispensed through specially certified pharmacies, according to the FDA.

In addition to this safety measure, the manufacturer will conduct 10 postmarketing studies, including the long-term CV outcomes trial suggested by the advisory panel to investigate the effect of extended-release phentermine/topiramate on risk for major adverse CV events, such as MI and stroke.

Researchers found that patients who did not lose at least 3% of their body weight after 12 weeks of treatment with extended-release phentermine/topiramate were unlikely to lose weight and maintain weight loss. For this reason, it is recommended that patients who have not lost at least 5% of their body weight after 12 weeks should discontinue use of the drug.

Based on data from clinical trials, patients with glaucoma or hyperthyroidism should not take extended-release phentermine/topiramate. Additionally, the drug is contraindicated for pregnant women, as it can cause harm to the fetus. Further, because the drug can increase heart rate, it use is also contraindicated for patients with recent or unstable CVD or stroke, and regular monitoring of heart rate is recommended for all patients.

The common side effects associated with the drug are parenthesis, dizziness, altered taste sensation, insomnia, constipation and dry mouth.

Perspective

Back to Top

Steven R. Smith, MD

This approval is really important for our patients, particularly from an endocrine perspective because obesity is the root cause in many other diseases that endocrinologists treat; diabetes being first on the list but not the only one. Many of us have been frustrated by the gap between diet and exercise recommendations and surgery, and this is now the second drug that allows us to start filling that gap. Between the approvals of lorcaserin (Belviq, Arena Pharmaceuticals) and phentermine/topiramate, this is probably one of the most important opportunities in diabetes management and obesity management we’ve had in the last 10 years.

Dosing medications is extremely difficult in the best of worlds. There is a dose selection here that really can provide some flexibility for physicians and patients and also the ability to say, “Let’s try this and see whether or not this is going to be helpful.” If it’s not helpful, drugs like this one should not be taken unless they have benefit. I think that is one of the areas in which the whole field has made advances.

With any obesity drug, we have to be careful to recognize that drugs do not work by themselves for obesity. Patients need to be ready to change; they need to use lifestyle modification as a foundation. These drugs can help patients be more effective in their lifestyle modification an increase their chance of success, but they don’t really substitute for people wanting to do something different in terms of their lifestyle. That is important. It sounds obvious on the surface, but for our endocrine family, we need to remember that this is an important aspect of this entire class of drugs.

Patient selection is also going to be really important. These drugs are not going to be for every obese patient, and there are obvious contraindications. There are patient populations where certain patients are going to do better than others. Being thoughtful about prescribing these medications is an important consideration. Choosing the right patient, building on success and getting comfortable with these medications is going to be a new area for endocrinologists, and I actually find that to be very exciting. This is an area where endocrinologists can make a difference and be thoughtful about how they approach the problem.

Steven R. Smith, MD

Scientific Director, Florida Hospital/Sanford-Burnham Translational Research Institute for Metabolism and Diabetes


Disclosures: Dr. Smith is a consultant for Amylin and Arena Pharmaceuticals, and has received research support from Orexigen.




ADD TOPIC TO EMAIL ALERTS


Receive an email when new articles are posted on

Please provide your email address to receive an email when new articles are posted on .


Subscribe

We were unable to process your request. Please try again later. If you continue to have this issue please contact [email protected]

Back to Healio

Phentermine And Topiramate (Oral Route) Proper Use

Proper Use

Drug information provided by: IBM Micromedex

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. If too much is taken, it may become habit-forming (causing mental or physical dependence).

This medicine comes with a Medication Guide. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Take this medicine once a day in the morning, with or without food. Avoid taking this medicine in the evening to prevent trouble sleeping.

Swallow the extended-release capsule whole. Do not crush, break, or chew it.

Carefully follow your doctor’s instructions for a reduced-calorie diet plan and regular exercise. Talk with your doctor before starting any exercise program.

Your doctor should tell you to stop taking this medicine if you do not lose a certain amount of weight within the first 12 weeks of treatment.

It is important that you drink extra water every day while you take this medicine to help prevent kidney stones.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.


  • For oral dosage form (extended-release capsules):


    • For weight loss:


      • Adults—At first, one tablet of 3.75 milligrams (mg) of phentermine and 23 mg of topiramate once a day for 14 days. After 14 days, your doctor may increase your dose to 7.5 mg of phentermine and 46 mg of topiramate once a day. Then, your doctor may increase your dose as needed up to 15 mg of phentermine and 92 mg of topiramate.

      • Children—Use is not recommended.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Portions of this document last updated: Aug. 01, 2021

Copyright © 2021 IBM Watson Health. All rights reserved. Information is for End User’s use only and may not be sold, redistributed or otherwise used for commercial purposes.


.

Does Topamax Work For Weight Loss

If there’s a way to safely drop lbs while relaxing on the couch and watching Real Housewives, that’s definitely something we want to know about.

Welp, some people say Topamax is that magic weight-loss bullet the world has been waiting for.

The drug was designed to treat and prevent seizures and migraines, but people who took it started to notice that they also lost weight on it. In fact, the makers of Topamax specifically list “weight loss” as a common side effect of taking the drug.

Still, this is a drug that’s made to help control seizures and migraines—not weight loss—which definitely raises a red flag if you’re thinking of taking it just to lose weight.

If You Take Topamax For Weight Loss, You’re Going Off-Label

The drug is approved by the Food and Drug Administration as being safe for treating seizures and migraines—but it’s not a drug that weight-loss physicians would usually recommend, says Peter LePort, M.D., a bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, Calif. “It’s a serious medication,” he says. “Whether it’s safe to use for dieting is really up in the air right now.”

Worth pointing out: Topamax comes with a bunch of other potential side effects that you really don’t want to mess with. We’re talking an increased risk of suicidal thoughts, vision problems that can lead to blindness, an increase in the level of acid in your blood (which can lead to soft bones and kidney stones), and birth defects if you take it when you’re pregnant.

Getty Images

People Who Take Topamax

Do Lose Weight—But There’s A Huge Catch

A few studies have looked at Topamax and weight loss. One, which was published in the journal Diabetes Research and Clinical Practice, analyzed existing research and found that Topamax led to an average of seven and a half pounds of weight loss in obese patients with type 2 diabetes. But—and this is a big but—it increased the likelihood that a patient would have “serious adverse events” like the side effects we mentioned above.

Another meta-analysis of 10 studies published in the journal Obesity Reviews found that obese patients lost an average of 12 pounds on Topamax, compared to those who took a placebo. Those who took the drug for 28 weeks or longer had more significant weight loss than those who took it for a smaller amount of time. But again, the study conclusion mentions that side effects need to be considered.

“This is not a weight loss that’s going to happen in a week or two.”

And a JAMA meta-analysis and review of several drugs that could cause weight loss found that Topamax led obese patients to lose at least 5 percent of their body weight after taking it for a year.

Worth pointing out: Topamax hasn’t been studied for weight loss in a long-term, double-blind, placebo-controlled trial, which is the gold standard for research. It’s also only been studied in people with obesity, so it’s hard to say how it might impact someone who just wants to drop a little weight. And, again, there are those side effects, which every study seems to warn about.

Another thing you should know: It would take some solid time to lose weight with this drug. “This is not a weight loss that’s going to happen in a week or two,” LePort says.

As for whether this could work for long-term weight loss, LePort says that “nobody really knows.” But, he points this out, “what has mostly been found with weight-loss medications is they may work while they’re being taken—but the idea is not to take them forever. A lot of patients gain the weight back after they stop taking it.”

Would It Be A Horrible Idea To Still Be Interested In Taking It?

Potential side effects are the biggie here. While plenty of people take Topamax for its intended purpose and have no issues, others have pretty major ones. Also, you need a prescription for this, and it’s pretty unlikely your doctor is going to love the idea of prescribing this for weight loss when it’s designed to treat other health conditions.

So…it’s probably best to talk to your doctor about other options.

Korin Miller
Korin Miller is a freelance writer specializing in general wellness, sexual health and relationships, and lifestyle trends, with work appearing in Men’s Health, Women’s Health, Self, Glamour, and more.

This content is created and maintained by a third party, and imported onto this page to help users provide their email addresses. You may be able to find more information about this and similar content at piano.io

Topiramate for Weight Loss and Eating Disorders

Eye problems can lead to permanent loss of vision if not treated. Tell your doctor beforehand if you’ve had glaucoma and report eye pain, redness, or vision changes during treatment.

Decreased sweating makes it more difficult for your body to cool down when it gets very hot and might make you more vulnerable to heat-stroke. Avoid exposure to heat, drink plenty of fluids, and notify your doctor if you have a fever.

Suicidal thoughts or actions should be reported immediately to your doctor, including panic attacks, agitation, irritability, anxiety, depression, sleep problems, talking or thinking about suicide, and any other changes in behavior or mood.

Excess acid in the blood (acidosis) can cause tiredness, loss of appetite, irregular heartbeat, and impaired consciousness, and is more likely if you consume a high-fat, low-carbohydrate diet or have kidney disease, respiratory problems, or diarrhea. Tell your doctor if you have any of those conditions before or during treatment, and don’t follow a high-fat, low-carb diet while taking the medication.

Kidney stones might develop. Drink six to eight glasses of water a day and tell your doctor beforehand if you’ve ever had kidney stones.

Cognitive problems involving thinking, concentration, attention, memory or speech might occur. Topiramate has also been found to cause confusion, dizziness, and sleepiness. Don’t drive a car or operate machinery until you know how the drug affects you, and avoid alcohol and sedating drugs.

Other side effects include headaches, tingling in the hands or feet, dry mouth, nausea, taste disturbance, diarrhea, upset stomach, and menstrual problems. Additionally, the FDA recently announced that Topamax can cause birth defects in humans.

Drug interactions include reduced effectiveness of birth-control pills. Tell your doctor what prescription and over-the-counter medications and supplements you are taking or plan to take.

Sudden withdrawal from topiramate can cause serious problems. Don’t stop taking it without first talking to a doctor.

Tell your doctor before treatment if you’ve ever had liver problems, osteoporosis, or mood disorders, or if you’re pregnant, planning to become pregnant or breast-feeding.

Phentermine/Topiramate (Qsymia) for Chronic Weight Management – STEPS

Phentermine/topiramate (Qsymia) combines a centrally acting appetite suppressant (phentermine) with an antiepileptic agent (topiramate) in an extended-release capsule. It is labeled for use as an adjunct to exercise and a reduced-calorie diet for chronic weight management in adults with a body mass index (BMI) of 27 kg per m2 or greater and at least one weight-related comorbidity, or with a BMI of at least 30 kg per m2.1 Phentermine/topiramate is a controlled substance (U.S. Food and Drug Administration [FDA] schedule IV).

SAFETY

Potential safety issues with phentermine/topiramate include nephrolithiasis, cardiac risk, and teratogenicity. In two 56-week randomized controlled trials with a total of more than 3,500 participants, patients taking phentermine/topiramate did not have more serious adverse events than those taking placebo, with one exception: 1% of patients taking the highest dose (15/92 mg) developed significant nephrolithiasis. Phentermine/topiramate does not increase symptoms of depression, even in patients with preexisting major depression. It does not increase the risk of arrhythmias, valve disease, or myocardial infarction, although studies to date excluded patients with known cardiac problems. Because patients had a dose-dependent increase in heart rate, the FDA is requiring postmarketing evaluation of cardiovascular safety. Phentermine/topiramate is an FDA pregnancy category X drug. In animal and human studies, topiramate has been associated with a risk of cleft lip.

TOLERABILITY

Phentermine/topiramate is well tolerated by most patients. Common side effects are dose dependent and include dry mouth, constipation, paresthesia, insomnia, irritability, and altered taste sensation. These effects typically develop in less than 10% of patients at the lowest dose (3.75/23 mg), 15% at the recommended dose (7.5/46 mg), and between 10% and 20% at the highest dose (15/92 mg). In clinical trials, patients taking phentermine/topiramate were less likely to drop out than patients taking placebo.

EFFECTIVENESS

Combining phentermine/topiramate with a reduced-calorie diet results in greater weight loss than combining reduced calories and increased activity. After one year of treatment, patients taking the maximum dose (15/92 mg) will have lost an average of 11% of their body weight, and those taking the lower dose (7. 5/46 mg) will have lost an average of 7% to 8% of their weight. To achieve 5% weight loss (the threshold for clinically meaningful weight loss), three to four patients need to be treated at the lower dose and two to three patients treated at the higher dose for 56 weeks for one additional patient to reach this threshold (number needed to treat [NNT] = 3 to 4, and NNT = 2 to 3, respectively). To achieve 10% weight loss, four to nine patients need to be treated at the lower dose and three patients treated at the higher dose for 56 weeks for one additional patient to reach this threshold (NNT = 4 to 9, and NNT = 3, respectively).

The benefit of this weight loss is not known. Over two years, systolic and diastolic blood pressure will be lowered by 3 to 5 mm Hg, and in patients with type 2 diabetes mellitus, A1C levels will be lowered by 0.2% to 0.4%.2 Patients with type 2 diabetes and those with hypertension may require less medication to control these conditions.2 Patient-oriented outcomes such as the development of osteoarthritis, diabetes, hypertension, and mortality have not been studied. It is unknown if weight loss is sustained after stopping the medication.

PRICE

A 30-day supply of phentermine/topiramate (3.75/23 mg) costs approximately $160. Other FDA-approved medications for the treatment of obesity include lorcaserin (Belviq; $213 for a 30-day supply), orlistat (Xenical; $470), and phentermine ($16).

SIMPLICITY

Patients should take phentermine/topiramate once a day in the morning, with or without food, to lessen the likelihood of insomnia. Patients are instructed to start at the lowest daily dosage (3.75/23 mg) and increase after 14 days to the target dosage (7.5/46 mg per day). If patients do not lose 3% of their body weight after 12 weeks, the dosage should be increased to 11.25/69 mg once daily for another 14 days before increasing to the maximum dosage of 15/92 mg per day. Patients should stop taking phentermine/topiramate after 12 weeks at this dose if they have not lost 5% of their body weight.

Women of childbearing age should have a negative pregnancy test before starting treatment and should continue to have monthly testing during treatment. They should use reliable contraception and discontinue treatment immediately if they conceive.1 Phentermine/topiramate can be dispensed only by certified pharmacies, whose pharmacists are required to give women appropriate counseling regarding pregnancy prevention. Physician training and a list of certified pharmacies are available online.3

Topamax (Topiramate) – Dr. Marlowe’s Weight Loss Institute. 411 Billingsley Rd, Suite 104.

How does Topamax help me lose weight?
Topamax works in multiple ways to help you lose weight, but you must change your behavior in response to those effects. In non-technical terms, it works on neurons in the brain to (1) decrease the addictiveness of food and also to (2) make you feel full sooner. It is great for people who are addicted to carbs, because it removes the pleasure you get from carbs. When that happens, you need to stop eating the carbs you no longer enjoy. It has been known to make foods like soda taste flat and wine/beer taste bad. You can get drunk, but you no longer get a happy buzz. They did a one-year study of alcoholics joining AA who were seriously trying to quit drinking and the ones who took Topamax did a significantly better job of staying clean and sober than the alcoholics who took placebo. Also, you get full on much less food. When that happens, you need to stop eating, because if you keep eating, you will feel bad reflux.

What are some side-effects?
Many patients experience side-effects from this medicine. Patients can have side-effects that are very annoying, but they usually slowly go away over a period of 2-5 weeks while you continue the medicine. You can prevent most side-effects by taking Euphasia two capsules twice daily to chase away the side-effects. Euphasia is available at our office. Sometimes, the side-effects don’t lessen and you must discontinue the Topamax entirely, and then the side-effects do go away. You may experience numbness/tingling of your fingers or toes, drowsiness, fatigue, and loss of appetite. You may temporarily experience difficulty concentrating, memory difficulties, difficulty finding the right word, diarrhea, constipation, mood disturbances/improvements, or sleep disturbance. Less commonly, Topamax can cause kidney stones, reflux if you overeat, or upper respiratory infections. If any of these happen, please let us know so we can discuss the risks and benefits of continuing the Topamax. If any vision changes happen, which is very rare, seek medical attention immediately. Don’t become pregnant while taking Topamax because Topamax is known to cause birth defects. This handout is not a substitute for the FDA’s handout, so please read the entire FDA insert.

What results have you seen at The Institute?
One patient said, “Dr. Marlowe, this is the first time I have been able to drive past the ‘Hot Now’ Krispy Kreme sign.” He lost more than 70 lbs on Topamax. Another said, “I haven’t had a soft drink in 6 months. Yesterday, I tried a Coke and it tasted TERRIBLE – like river water. That medicine is great.” Another said, “This is WONDERFUL. I didn’t know what it felt like to never have a migraine. I’ve had them my whole life. Now I know what it feels like to be free.” Yet another, “My head felt funny. I felt disoriented. I didn’t know where I was for a few seconds. My tongue felt heavy. It was awful.” Someone else, “People said I slurred my words.” A different patient, “I couldn’t say the word I knew – words were always on the tip of my tongue.” Or: “I can’t remember stuff and I was foggy, but it was worth it and I tell my friends who I send to Dr. Marlowe to stick with Topamax, because I went from 210 to 155 lbs.”

How do I take Topamax?
Take one pill at bedtime for 10 days. The next 10 days, take one in the morning and one at night. The next 10 days, take one in the morning and two at night. If you develop mild side-effects, continue increasing the dose. If the side-effects are tolerable, don’t increase the dose, but start the Euphasia described above. If the side-effects are intolerable, please discontinue the Topamax and call our office. If the side-effects create an emergency, call 911.

Why don’t you just prescribe Qsymia?
Qsymia is the combination of phentermine and Topamax into one pill. I rarely prescribe it. First, if you need lower or higher doses of phentermine or Topamax, you can’t do it with Qsymia. The doses are not adjustable. When Topamax and phentermine are separate pills, we can adjust either one. Second, Qsymia is far more expensive and could cost you 10 times as much. Lastly, if you started a combination-pill like Qsymia and broke out in an allergic rash, you wouldn’t know which ingredient you were allergic to, so you wouldn’t be allowed to take either medication ever again.

Memorial Sloan Kettering Cancer Center

This document, provided by Lexicomp ® , contains all the information you need to know about the drug, including the indications, route of administration, side effects and when you should contact your healthcare provider.

Trade names: USA

Qudexy XR; Topamax; Topamax Sprinkle; Trokendi XR

Trade names: Canada

ACH-Topiramate; AG-Topiramate; APO-Topiramate; Auro-Topiramate; DOM-Topiramate; GLN-Topiramate; JAMP-Topiramate; Mar-Topiramate; MINT-Topiramate; MYLAN-Topiramate; PMS-Topiramate; PRO-Topiramate; RAN-Topiramate [DSC]; SANDOZ Topiramate; TEVA-Topiramate; Topamax; Topamax Sprinkle

What is this drug used for?

  • Used to treat seizures.
  • It is used for the prevention of migraine.
  • This medicinal product can be used for other indications. Consult your doctor.

What should I tell my doctor BEFORE taking this drug?

  • If you are allergic to this drug, any of its ingredients, other drugs, foods or substances. Tell your doctor about your allergy and how it manifested itself.

Combination of this drug with certain medications and medical conditions may be adverse.

Tell your doctor and pharmacist about all the medicines you take (both prescription and over-the-counter, natural products and vitamins) and your health problems. You need to make sure that this drug is safe for your medical conditions and in combination with other drugs you are already taking. Do not start or stop taking any drug or change the dosage without your doctor’s approval.

What do I need to know or do while taking this drug?

  • Avoid driving or other activities that require increased attention until you see how this drug affects you.
  • Less sweating and a significant increase in body temperature have happened with this drug. In some cases, patients required hospital treatment. Caution should be exercised in hot weather and during physical activity.Call your doctor right away if your body temperature rises or you don’t sweat during exercise or in hot weather.
  • Like other drugs for the treatment of seizures, this drug in rare cases may increase the risk of suicidal ideation or behavior. This risk may be higher in people who have attempted suicide or have had suicidal thoughts in the past. See your doctor right away if you develop or worsen symptoms such as depression, nervousness, anxiety, irritability, panic attacks, or other mood or behavior disorders. In case of suicidal thoughts or attempted suicide, contact your doctor immediately.
  • This drug may cause an acidic disorder in the blood (metabolic acidosis). This effect is more likely to occur in children and in people with kidney, respiratory or diarrhea problems. The likelihood also increases if you are taking certain other medicines, have had surgery, or are on a ketogenic diet. Over time, metabolic acidosis can cause kidney stones, bone disorders, and growth disorders in children.
  • This drug may increase the risk of bleeding. Sometimes bleeding can be life-threatening. Consult your doctor.
  • This drug may cause very serious eye problems. Left untreated, these problems can lead to long-term vision loss. Call your doctor right away if you develop new symptoms of eye problems, such as blurry or other visual disturbances, or redness of the eyes.
  • Possible severe skin reaction (Stevens-Johnson syndrome / toxic epidermal necrolysis).This can lead to serious and permanent health problems and sometimes death. Get immediate medical attention if you experience symptoms such as redness, skin swelling with blistering or scaling (with or without a high fever), eye redness or irritation, or ulceration in the mouth, throat, nose, or eyes.
  • If the patient is a child, use this medication with caution. In children, the risk of some side effects may be higher.
  • In some cases, the drug may affect the growth rate in children and adolescents. They may need to check their growth rate regularly. Consult your doctor.
  • The effectiveness of birth control pills and other hormonal contraceptives may be reduced. Use a different type of birth control, such as a condom, while taking this drug.
  • If you are using hormonal contraception and have any changes in your period, consult your doctor.
  • When used during pregnancy, the drug may have a harmful effect on the fetus. If you are pregnant or become pregnant while taking this drug, call your doctor right away.
  • If you can get pregnant but don’t want to, use birth control while taking this drug.
  • Tell your doctor if you are breastfeeding. It is necessary to consult if the drug poses any risk to the child.

What side effects should I report to my doctor immediately?

WARNING. In rare cases, some people with this drug can have serious and sometimes deadly side effects. Call your doctor or get medical help right away if you have any of the following signs or symptoms, which may be associated with serious side effects:

  • Signs of an allergic reaction such as rash, hives, itching, reddened and swollen skin with blistering or scaling, possibly associated with fever, wheezing or wheezing, tightness in the chest or throat, difficulty breathing, swallowing or speaking, unusual hoarseness, swelling in the mouth, face, lips, tongue, or throat.
  • Symptoms of increased blood acidity (acidosis), such as confusion, rapid breathing, tachycardia, irregular heartbeat, very severe abdominal pain, nausea or vomiting, severe drowsiness, shortness of breath, increased fatigue or weakness.
  • Signs of infection such as fever, chills, very severe sore throat, ear, or sinuses, cough, increased or discolored phlegm, pain when urinating, mouth ulcers, or an open wound.
  • Signs of high ammonia levels, such as irregular heartbeat, trouble breathing, confusion, pale skin, bradycardia, seizures, sweating, vomiting, or muscle twitching.
  • Any unexplained bruising or bleeding.
  • Feeling confused, unable to concentrate, or changes in behavior.
  • Violation or loss of memory.
  • Difficulty speaking.
  • Sleep disorders.
  • Balance change.
  • Severe dizziness or fainting.
  • If it is impossible to eat.
  • Back pain, abdominal pain or blood in the urine. Perhaps these are signs of kidney stones.
  • Unusual burning, numbness, or tingling sensations.
  • Bone pain.
  • Chest pain.
  • Muscle pain or weakness.
  • Shiver.
  • Difficulty walking.
  • Loss of control over eye movements.
  • Liver problems have rarely happened with this drug.Sometimes these cases were fatal. Call your doctor right away if you have signs of liver problems such as dark urine, tiredness, lack of appetite, nausea or abdominal pain, discolored stools, vomiting, yellowing of the skin or eyes.

What are some other side effects of this drug?

Any medicine can have side effects. However, many people have little or no side effects.Call your doctor or get medical help if these or any other side effects bother you or do not go away:

  • Constipation, diarrhea, abdominal pain, nausea, vomiting, or decreased appetite.
  • Changes in the ability to perceive taste.
  • Weight loss.
  • Nervous tension and agitation.
  • Feeling dizzy, sleepy, tired, or weak.
  • Headache.
  • Hyperemia (blush).
  • Signs of a cold.
  • Joint pain.

This list of potential side effects is not exhaustive. If you have any questions about side effects, please contact your doctor. Talk to your doctor about side effects.

You can report side effects to the National Health Office.

You can report side effects to the FDA at 1-800-332-1088. You can also report side effects at https: // www.fda.gov/medwatch.

What is the best way to take this drug?

Use this drug as directed by your healthcare practitioner. Read all the information provided to you. Follow all instructions strictly.

All forms of issue:

  • Take this medication with or without food.
  • Continue taking this drug as directed by your doctor or other healthcare professional, even if you feel well.
  • Do not stop taking this drug abruptly without talking to your doctor. This can increase the risk of seizures. If necessary, this drug should be stopped gradually as directed by your doctor.
  • Drink plenty of decaffeinated fluids, unless your doctor tells you to drink less fluids.
  • Tell all healthcare providers that you are taking this drug. These are doctors, nurses, pharmacists and dentists.
  • Perform blood tests as directed by your doctor. Please consult your doctor.
  • Consult your doctor before using marijuana, other forms of cannabis, prescription or over-the-counter drugs that may slow you down.
  • Taking this drug with valproic acid may cause a decrease in body temperature. It can also cause fatigue, confusion, or coma.Consult your doctor.

Tablets:

  • Swallow whole. Do not chew, break, or crush.
  • Avoid drinking alcohol while taking this drug.

Normal-release and slow-release capsules to open:

  • You can swallow it whole or sprinkle the contents into a tablespoon with a soft food such as applesauce.Do not crush or chew the drug.
  • If taken mixed, swallow immediately. Do not store for future use.
  • To be sure you have swallowed the drug, drink the liquid immediately after consuming food with the added drug.
  • Avoid drinking alcohol while taking this drug.

Sustained-release capsules:

  • Swallow whole.Do not chew, open, or crush.
  • Do not add this drug to food.
  • Avoid drinking alcohol while taking this drug. It is especially important not to drink alcohol within 6 hours before or 6 hours after taking this drug.

What should I do if a dose of a drug is missed?

Sustained-release capsules:

  • Call your doctor for further instructions.

Sustained-release capsules to open:

  • Take the missed dose as soon as you can.
  • If it is time for your next dose, do not take the missed dose and then return to your normal dose schedule.
  • Do not take 2 doses at the same time or an additional dose.
  • If you miss 2 doses, call your doctor.

All other dosage forms:

  • Take the missed dose as soon as you can.
  • If there are less than 6 hours before your next dose, do not take the missed dose and go back to your usual schedule.
  • Do not take 2 doses at the same time or an additional dose.
  • If you miss 2 doses, call your doctor.

How do I store and / or discard this drug?

  • Store at room temperature, protected from light. Store in a dry place. Do not store in the bathroom.
  • The lid must be tightly closed.
  • Store all medicines in a safe place. Keep all medicines out of the reach of children and pets.
  • Dispose of unused or expired drugs. Do not empty into toilet or drain unless directed to do so. If you have any questions about the disposal of your medicinal products, consult your pharmacist. Your area may have drug recycling programs.

General information on medicinal products

  • If your health does not improve or even worsens, see your doctor.
  • You should not give your medicine to anyone and take other people’s medicines.
  • Some medicines may have different patient information sheets. If you have questions about this drug, talk with your doctor, nurse, pharmacist, or other healthcare professional.
  • A separate patient instruction sheet is attached to the product. Please read this information carefully. Reread it every time you replenish your supply. If you have questions about this drug, talk with your doctor, pharmacist, or other healthcare professional.
  • If you think there has been an overdose of a drug, call a Poison Control Center immediately or seek medical attention. Be prepared to tell or show which drug you took, how much and when it happened.

Use of information by consumer and limitation of liability

This information should not be used to make decisions about taking this or any other drug. Only the attending physician has the necessary knowledge and experience to make decisions about which drugs are suitable for a particular patient. This information does not guarantee that the drug is safe, effective, or approved for the treatment of any disease or specific patient. Here are only brief general information about this drug. It does NOT contain all available information on the possible use of the drug with instructions for use, warnings, precautions, information about interactions, side effects and risks that may be associated with this drug. This information should not be construed as a treatment guide and does not replace information provided to you by your healthcare professional. Check with your doctor for complete information on the possible risks and benefits of taking this drug.Use of this information is governed by the Lexicomp End User License Agreement available at https://www.wolterskluwer.com/en/solutions/lexicomp/about/eula.

Copyright

© UpToDate, Inc. and its affiliates and / or licensors, 2021. All rights reserved.

90,000 Effective slimming drug | Let’s lose weight!

Phentermine belongs to a class of drugs called “anorectics”, also known as appetite suppressants.Taking it helps suppress appetite, thereby limiting the amount of calories consumed. Over time, this can lead to weight loss, according to publication Let’s Lose Weight!

Although the exact mechanisms of action of phentermine remain unclear, the drug is believed to work by increasing levels of neurotransmitters in the brain. They are your body’s chemical messengers and include norepinephrine, serotonin, and dopamine.

When your levels of these three chemicals increase, your hunger will decrease.However, you can build up a tolerance for the appetite suppressant effects of phentermine over a period of several weeks. In this case, you should not increase the dose of the drug, but stop using it completely.

Several clinical studies have shown that it can increase fat loss. Average weight loss expected with use is 5% of your starting body weight. However, within 12 weeks it can be as high as 10%. This corresponds to a loss of 4.5–9 kg for a person weighing 90.7 kg.

In a meta-analysis of six studies, people who took an average dose of 27. 5 mg of phentermine for 13 weeks lost 6.3 kg, compared with 2.8 kg in the placebo groups.

The drug is effective for weight loss, but it may work better when combined with topiramate.

Topiramate itself is used to treat seizures, but like phentermine, it also has appetite-reducing properties.

Topiramate and Phentermine is a combination drug marketed under the brand name Qsymia.

Compared with the other three commonly prescribed weight loss drugs, the combination of phentermine and topiramate was associated with the highest chances of losing at least 5% of initial body weight. What’s more, studies show that this combination is the most effective for weight loss to date – people achieve an average weight loss of 9.8 kg after taking the maximum dose for one year.

To learn more about healthy eating, diets and new scientific research, put LIKES and SUBSCRIBE to our channel Let’s Lose Weight!

✔ remove belly day at home

Key tags: best exercises for fast weight loss, where to buy remove belly day at home, laxative diet pills.


how to remove a belly with honey, buy spirulina in diet pills, excess weight from resentment, breakfasts for weight loss, individual weight loss

What is to remove the belly day at home

I completely agree with all the good reviews about Keto Light for weight loss. These capsules deserve all the respect and praise. They contain natural ingredients, act gently, do not cause side effects and disruptions in the body.Fat deposits disappear evenly from all problem areas, weight decreases gradually, but reliably. My assessment of the drug is 5+. Do not use questionable options for weight loss – they are unreasonably expensive and unsafe. Buying Keto Light on the official website will allow you to permanently get rid of extra pounds, shape your figure, and improve your health. This is the right drug because it is not only effective but also harmless.

Official website to remove belly day at home

Composition

The easiest way to remove the belly and lose weight without a diet is to eat fractionally. After 2-3 days, the waist will become noticeably thinner. Gradually, the body will get used to eating on time, small portions will be enough for the stomach, while the arrow of the scales will rapidly move downward. To get an attractive flat stomach, many live in the fitness room and crunch cabbage leaves, washed down with probiotics. No questions asked: this is a healthy and correct path to physical perfection. Before you remove your belly with diets at home in 3 days, it is recommended to study contraindications – a strict diet is not suitable for everyone.It is forbidden to tighten problem areas with strict diets for diseases of the digestive organs (gastritis, ulcers, colitis), serious. Remove belly fat in 2 weeks – simple tips to help you lose weight. A morning walk can be replaced with light exercise at home. Eating eggs will help reduce subcutaneous fat and flatten your belly. Of course, it is impossible to find a dream figure in a matter of days – you need to work on this for a long time and persistently, if nature has not awarded you with excellent physical data, or you have lost them for some reason. What to do and how to eat to remove the belly yourself at home. We count calories. How many calories do you need per day to lose weight. With a BMI of 18.5 – 29, all that is needed to remove the belly (if any) and lose weight on your own at home is a diet, proper nutrition. In order for a healthy woman to tighten her belly in 1 day at home, motivation is needed – without some. If you have to remove the stomach very quickly, it is strongly not recommended to eat after 18 hours. And even sitting down to the table before the time limit comes, you need to try.Fasting day to remove the belly. The body requires periodic rest, so don’t forget. How to quickly remove the belly with a wrap. The most effective weight loss at home is the vinegar wrap. The product evaporates quickly, cooling the skin and keeping it warm. You can quickly remove the belly in summer and autumn, when fruits and vegetables are abundant. Only absolutely healthy people who do not have chronic diseases can take baths and do wraps at home. Slimming baths are taken while sitting, water should be.

Test results

Keto Light Weight Loss Means control appetite and energize the whole day. By accelerating metabolism, it is possible to start the process of burning fat cells. The effectiveness of the breakdown of fats is ensured by the fruit acids included in the composition. In addition to the listed components, the composition of the Keto Light slimming capsules contains other components of natural origin.The composition has undergone a large-scale laboratory study. According to the results of the examination, the agent does not cause side effects, it is suitable for use even in the presence of concomitant pathologies: diabetes mellitus, hypertension, arrhythmias.

Expert opinion

Keto Light is not intended for purchase in offline stores or pharmacies. By this measure, the manufacturer limited potential customers from purchasing capsules at an inflated price. In addition, ordering through intermediaries increases the risk of receiving a substandard product.

Topiramate for weight loss is started at a dose of 25 mg per day, then increased to a clinically effective dose of 25 mg every two weeks. The average daily dose is usually 200 mg per day in two divided doses, duration. Topiramate is a powerful antidepressant, the use of which in reasonable doses allows it to be used in the fight against excess weight, in particular, with obesity. This remedy is used as a fat burner, as well as a drug that can overcome eating disorders: inability.Phentermine and Topiramate | A new method to lose weight and restore metabolism. The drug for reducing appetite – Phentermine. The first drug from this combination remedy for weight correction is Phentermine (Adipex, Duromine, Mirapront, Ionamin, Lonamin, Omnibex, etc.). He belongs to the group. Topiramate for weight loss dosage. Nimby: CLA Mia: 2.5 !!!. Topiramate was synthesized in a year by researchers Bruse Marianoff and Joseph Gardocki during the creation of a new group of antidiabetic, hypoglycemic agents. Now, it’s time for us to study another crazy drug for weight loss, namely Topiramate (patented as Topamax. Before reading, I strongly recommend that you study in the Handbook (link) the combined annotation on this pharmacological. The reasons why topiramate reduces weight remain Several theories are considered: Loss of taste associated with decreased saliva Topiramate is effectively eliminated by hemodialysis Prolonged hemodialysis may result in a decrease in blood topiramate concentration below the amount required to maintain anticonvulsant activity.Topiramate is an antiepileptic drug with an unusual structure and is a fructose derivative. Topiramate, marketed under the brand name Topamax, is a medicine, among others. decreased weight, biting price. I have been sick since the age of 15-16. The attacks are rare. For the last five years I have been treated with Topamax (Maxitopyr). There are no attacks for 5 years (ugh ugh ugh). The dose was reduced to 50 mg per day. The drug itself is heavy – I lost weight on it before. From a medical point of view, weight may be extra only for the body and its work, but not at all for its self-esteem.Let’s dig deeper and see where excess weight comes from. To do this, let’s go over the path that food takes on the way to body fat. Absorption. Reviews of Topiramate from patients and users of BabyBlog. Indications for use, description of side effects and possible harm during pregnancy and lactation. Opinions of doctors and patients.

Assignment

Due to the fact that today many people are overweight, the drug is in great demand.It is bought by both women and men. Reviews after a course of weight loss, many of them leave on the official resource of the manufacturer. We also receive words of gratitude to the address of the manufacturer on our e-mail.

Diet pills are the last resort to resort to. But you need to drink it for a very long time to feel the effect. Let’s go through their assortment and find out which pills are effective and which are not: 1. Reduxin. The basis for successful weight loss is not weight loss drugs, but the normalization of the lifestyle: balanced hypocaloric nutrition, sports.Slimming drugs, for example, based on Orlistat, as well as other slimming drugs, including. Diet pills are the most effective weight loss drugs. By far the most effective diet pills are evidence-based drugs. They have been studied up and down. Have a clear, predictable result. I drank a special pill (capsule or powder) and lost weight. But in reality, not everything is as simple as obese patients believe.Choosing good diet pills is not easy. It would seem that they came to the pharmacy and asked to sell you the most effective anti-obesity drug, success is guaranteed. Diet pills are the easiest and most affordable way to lose weight without tormenting your own. Losing weight is a very long and painstaking process. To get the maximum effect from taking drugs, you must: limit the use of fatty and spicy foods; try. You must drink 1 tablet within 30 days. To speed up the process, add green tea or to your diet.Microcrystalline cellulose is a weight loss drug that comes in the form of tablets or powder. Often, MCC is produced in its pure form, but sometimes. Diet pills: appetite suppressants, anti-fat pills, – an overview of popular diet pills and aids. Whether it is necessary to make a choice – slimness or health, and whether there is a reasonable balance, read our material. Having decided to use the help of the pharmacy slimming products. You can drink weight loss medicines only after making sure that the reason for the excess weight is exactly.You need to take these diet pills three times a day with meals. If in three months the weight has decreased by no more than 5% from the initial one, further use of the drug should be discontinued. You need to take two capsules before eating (half an hour), drinking them clean. KRKA is a trusted supplier of diet pills. I recommend downloading the Nike training app and drinking Keto Light tablets, which will help you stay in shape and with proper nutrition in general. What diet pills are there? Each drug has a different effect on the body.Pharmaceutical diet pills are strong enough before taking them. Orsoten. What pills do you need to drink to lose weight? Orsoten is the most effective remedy in which. Slimming drugs from the pharmacy that really help !. The ideal is fast weight loss pills that are harmless to. Not a single strong fat-burning drug can lead to the desired result, if you continue to eat fast foods in parallel, increase it.

How to order?

Fill out the form for consultation and order to remove the belly day at home.The operator will clarify all the details with you and we will send your order. In 1-10 days you will receive the parcel and pay for it upon receipt.

remove belly day at home . how to calculate kbzh for weight loss calculator. Reviews, instructions for use, composition and properties.

Women are always in pursuit of harmony, even having ideal parameters, they always find something to change and improve in themselves. Diet with soda for weight loss To quickly lose weight, you can include a drink of soda and apple cider vinegar in the diet menu.Reception of such a means for losing weight is carried out daily, but it can. Most recently, the World Information Network was blown up by articles on the topic: how to lose weight with baking soda in 3 days by 10 kg. A popular means of losing weight is soda. The same soda that is added to baked goods and used to disinfect and clean dishes. The use of soda for weight loss should be extremely careful. This product really helps you lose weight. In search of an answer to the question What to eat to lose weight? people are ready to use sometimes very strange in taste and appearance products.The result is a gradual weight loss, improved metabolic processes. Wonderful baths with soda for weight loss: recipes and expected results. Losing weight with soda is a way for the lazy and busy. Its main advantage: you do not have to suffer from a rigid diet or large physical. Baking soda (sodium bicarbonate or sodium bicarbonate) is highly sought after worldwide. Slimming soda. Losing weight with baking soda attracts with its ease. No hungry diets or exhausting exercise.You will learn from the article. Soda helps to lose weight – this is what many losing weight say who have already tried this remedy.

Official website to remove belly day at home

✔ You can buy and remove your belly at home in such countries as:

Russia, Belarus, Kazakhstan, Kyrgyzstan, Moldova, Uzbekistan, Ukraine Armenia

Do not use dubious options for weight loss – they are unreasonably expensive and unsafe …Buying Keto Light on the official website will allow you to permanently get rid of extra pounds, shape your figure, and improve your health. This is the right drug because it is not only effective but also harmless. Women are always in pursuit of harmony, even with ideal parameters, they always find something to change and improve in themselves. Diet with soda for weight loss To quickly lose weight, you can include a drink of soda and apple cider vinegar in the diet menu. Reception of such a means for losing weight is carried out daily, but it can.Most recently, the World Information Network was blown up by articles on the topic: how to lose weight with baking soda in 3 days by 10 kg. A popular means of losing weight is soda. The same soda that is added to baked goods and used to disinfect and clean dishes. The use of soda for weight loss should be extremely careful. This product really helps you lose weight. In search of an answer to the question What to eat to lose weight? people are ready to use sometimes very strange in taste and appearance products.The result is a gradual weight loss, improved metabolic processes. Wonderful baths with soda for weight loss: recipes and expected results. Losing weight with soda is a way for the lazy and busy. Its main advantage: you do not have to suffer from a rigid diet or large physical. Baking soda (sodium bicarbonate or sodium bicarbonate) is highly sought after worldwide. Slimming soda. Losing weight with baking soda attracts with its ease. No hungry diets or exhausting exercise.You will learn from the article. Soda helps to lose weight – this is what many losing weight say who have already tried this remedy. Keto Light Weight Loss Means control appetite and energize all day long. By accelerating metabolism, it is possible to start the process of burning fat cells. The effectiveness of the breakdown of fats is ensured by the fruit acids included in the composition.

I completely agree with all the good reviews about Keto Light for weight loss. These capsules deserve all the respect and praise.They contain natural ingredients, act gently, do not cause side effects and disruptions in the body. Fat deposits disappear evenly from all problem areas, weight decreases gradually, but reliably. My assessment of the drug is 5+.

I was looking for an inexpensive but effective weight loss product on the Internet and chose Keto Light. Why? It has a low price, it contains natural ingredients and many people wrote praise about it. I took capsules for 3 months and made sure that everything good that they write about them is true.Indeed, during this time I have lost almost 30 kilograms and although I do not adhere to any diet, I do not gain weight back.

Employees of the manufacturer of the Keto Light product commented on all 4 aspects. The low cost is due to the manufacturer’s focus on serving customers with different budgets. Thanks to an adequate price for a fat-burning drug, everyone can safely lose weight, regardless of income. This simultaneously increases the income of the manufacturer, since customers with a modest budget are in the majority.

Topiramate: on the use of the drug in medical practice

INTRODUCTION

Epilepsy is one of the most common neurological diseases. In the United States alone, 150,000 new cases of the disease are registered annually [1]. According to the forecasts of the World Health Organization (WHO) [2], seizures in the near future will be recorded in 1 in 20 people at least once in a lifetime, and epilepsy will be diagnosed in at least 1 in 200 inhabitants.Despite the fact that the quality of life of most patients is significantly improved against the background of mono- or combination therapy with antiepileptic drugs (AEDs), 30–40% of them continue to experience seizures [3]. It becomes obvious that it is necessary to introduce new AEDs, which have both high efficiency and good tolerance for long-term use. These drugs include topiramate, which was approved for use in children and adults in 1997. Currently, there are several generic topiramate drugs on the market, including Topsaver.

ACTION MECHANISM

Topiramate (Topsaver) has several mechanisms of action, mutually complementing each other [4]. First of all, the drug blocks voltage-dependent sodium channels and suppresses the emergence of repeated action potentials against the background of prolonged depolarization of the neuron membrane. This effect is enhanced by the ability of topiramate to facilitate GABA-dependent inhibition of neurons by enhancing the action of GABA on GABAA receptors and increasing the flow of chlorine ions into the cell.At the same time, the drug inhibits the excitation of glutamine AMPA / KA receptors by kainate (kainate is a subtype of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors), practically without affecting NMDA receptors. In addition, topiramate inhibits some isoforms of carbonic anhydrase, but the pharmacological effect of the blockade is much weaker than that of acetazolamide.

PHARMACOKINETICS

Topiramate is rapidly absorbed in the intestine, the maximum concentration is reached 2 hours after ingestion, bioavailability is about 80% and does not depend on food.Serum protein binding 13-17%. The half-life after a single and multiple doses is 21 hours, is metabolized by 30% in the liver (hydrolysis, hydroxylation, glucuronization), 70% is excreted unchanged in the urine. Plasma clearance is about 20-30 ml / min. Linear kinetics is observed at a daily dose of 200–800 mg. Stationary concentration with normal renal function is achieved after 4–8 days of regular administration of topiramate. Phenytoin and carbamazepine lower the content of topiramate in the blood.Kinetic interactions with other antiepileptic drugs are practically not expressed [5].

The need for monitoring the concentration of topiramate in the blood is much less pronounced than when using old AEDs, since the drug has a wide therapeutic range and linear kinetics [6].

APPLICATION OF TOPIRAMAT

Epilepsy

Topiramate is a modern AED, which is included in the recommendations of Western Europe and the United States for the treatment of partial and generalized seizures [7].The effectiveness of topiramate in epilepsy has been shown in randomized trials.

A double-blind, placebo-controlled study (n = 181) compared the effect of topiramate with placebo when added to the prescribed therapy (1-2 AEDs) in patients with refractory partial seizures. As a result, the reduction in the number of seizures significantly decreased by 30, 48 and 45%, respectively, with the appointment of 200, 400 and 600 mg / day of topiramate, while against the background of placebo, this indicator was 13%.The number of patients who responded to treatment (a decrease in the number of seizures by 2 times or more) in the topiramate group was 27, 47 and 46%, respectively, with the appointment of 200, 400 and 600 mg / day, in the placebo group these were 18%. The use of topiramate also significantly reduced the number of secondary generalized seizures. Adverse reactions were observed in 9% of patients in the topiramate group and in 7% of patients in the placebo group [8].

A similarly designed placebo-controlled study (n = 190) examined the effect of higher doses of topiramate on epilepsy with refractory partial seizures compared with placebo.During 18 weeks of treatment, the total number of seizures in patients decreased by 41% with the appointment of 600 or 800 mg of topiramate and by 38% with the use of 1000 mg of topiramate per day. With placebo, the number of convulsive episodes was reduced by only 1%. The response rate to topiramate treatment was 44%, 40% and 38% when 600, 800 or 1000 mg of the drug were used per day, respectively; in the placebo group, 9% of patients responded to treatment [9]. The effectiveness of topiramate as part of combination therapy for refractory partial epilepsy has been confirmed to date in a number of other comparative trials [10].

Three randomized, double-blind, placebo-controlled trials evaluated the anticonvulsant activity of topiramate as a monotherapy in newly diagnosed epilepsy. In these studies, it was shown that topiramate at a dose of 50-400-500 mg / day dose-dependently reduces the frequency of epileptic seizures and lengthens the time to the development of the first seizure from the start of treatment. When comparing topiramate (200 mg / day) with carbamazepine (600 mg / day) and valproate (1250 mg / day), it turned out that all drugs to the same extent, without significant statistical differences, reduce the number of epileptic seizures, in particular, a 6-month unapproachable period while taking all drugs was observed in the study in 44% of patients [11].

In a recent open-label study, it was found that topiramate can act as an alternative to valproate in adolescents and adult patients with epilepsy in the case of low efficacy or poor tolerance of the latter [12]. Topiramate was added to the received therapy with valproate, the dose was titrated to 50-200 mg / day. Valproate will then be discontinued and patients will receive topiramate instead. As a result, 70% of patients were successfully transferred to monotherapy with topiramate at an average daily dose of 150 mg / day.Of these, 75% achieved more than half the reduction in the number of epileptic seizures. In all patients, according to the special questionnaire QOLIE-10, the quality of life significantly improved in comparison with the period before treatment with topiramate. Side effects were reported in less than 5% of patients.

The effectiveness of topiramate as an adjunctive therapy in the treatment of children with Lennox-Gastaut syndrome (a serious illness in children 2–8 years old, characterized by the presence of various forms of epileptic seizures, diffuse slow peak-wave complexes in the interictal period and mental retardation) has been shown.In one study, adding topiramate at an average dose of 6 mg / kg / day to the received AEDs in 33% of patients decreased the number of large seizures by half or more [13].

Migraine

The effectiveness of topiramate in the prevention of migraine attacks in adults (with and without aura) was shown in two large studies, in which a total of 937 patients took part [14]. These studies have demonstrated that taking topiramate at a dose of 100-200 mg / day leads to a significant decrease in the frequency of migraine headache attacks in comparison with placebo (p <0.001).Topiramate improves the course of the disease, thereby increasing the quality of life of patients, as demonstrated using specially designed rating scales [15].

Schizophrenia

A placebo-controlled study has shown the efficacy of topiramate as an adjunct in schizophrenia in patients aged 18–45 years. A clinically significant response to treatment (more than 20% reduction on the PANSS positive and negative symptom scale) was observed in 50% of patients, while in the control group only in 12.5% ​​[16].

Alcoholism

The positive therapeutic effect of topiramate in the treatment of alcohol dependence is based on the ability of the drug to enhance GABAergic transmission and block the negative effects of glutamate in the corticomesolimbic system. In a recent double-blind, placebo-controlled study involving 371 patients aged 18–65 years, topiramate at a dose of 300 mg / day was shown to reduce the number of drinking days by 8.44% (p = 0.002) [17].Analysis of published studies has shown that the possibility of using topiramate in the treatment of alcoholism seems to be quite promising, therefore, it is necessary to conduct studies aimed at clarifying the specifics of the drug’s prescription and dosage regimen [18].

TOLERANCE OF TOPIRAMAT

In clinical studies, it was found that topiramate is generally well tolerated. Since the drug belongs to new AEDs, its study and implementation into practice were carried out taking into account the current high requirements for drug safety.Most often, when taking topiramate, drowsiness, dizziness, ataxia, nervousness, and fatigue are noted. Less commonly, memory loss, nystagmus, and body weight loss are possible. Side effects are mainly observed with the use of high doses of topiramate (600 mg / day or more), as well as with rapid titration of the dose of the drug [19].

There is information about the possibility of developing nephrolithiasis when taking topiramate. Probably, the formation of kidney stones is due to the fact that topiramate is a weak inhibitor of carbonic anhydrase.Blocking this enzyme leads to a decrease in citrate excretion and an increase in urine pH. The risk group for nephrolithiasis and its exacerbations includes patients with urolithiasis (including a family history).

Topiramate can reduce the effectiveness of combined oral contraceptives by reducing the level of estrogen, although the risk of such a complication is low and is observed with the use of high doses of the drug. Thus, in the study by D.R. Doose et al. [20] the combined use of a combined oral contraceptive (norethindrone + ethinyl estradiol) and topiramate at a dose of up to 200 mg / day did not lead to a decrease in the effect of the estrogenic and progestogenic components.Nevertheless, the attention of patients should be drawn to the risk of a decrease in the effect of contraception, a change in the nature of menstrual bleeding.

According to the FDA classification of medicines during pregnancy, topiramate belongs to category C – there have been no adequate and well-controlled studies on the use of the drug during pregnancy. The use of the drug is possible only if the expected effect of therapy outweighs the potential risk to the fetus.

TOPIRAMATE DOSING MODE

According to current recommendations [5], it is advisable to gradually titrate the dose of topiramate, which helps to minimize the development of side effects.Usually, adults are advised to take an initial dose of 25-50 mg / day, with a further increase in the dose by 25-50 mg / day every week until the optimal therapeutic effect is achieved. The target average dose of topiramate is considered to be 400 mg / day, divided into two doses. Smaller doses of the drug (200 mg / day) in studies have an unstable effect. The efficacy and safety of topiramate in a daily dose of more than 1600 mg has not been studied.

In children 2–16 years old, the target dose is 5–9 mg / kg / day in two doses.The initial dose should be 25 mg / day (or less) once at night during the first week of treatment, then the dose can be increased every 1-2 weeks by 1-3 mg / kg / day [21].

CONCLUSION

So, topiramate (Topsaver) is a modern remedy that can be used for some neuropsychiatric diseases. First of all, the drug is highly effective both in mono- and in combination therapy of epilepsy in adults and children, including those with resistant forms of the disease.The advantages of topiramate include beneficial pharmacodynamic and pharmacokinetic characteristics: a complex mechanism of action, high bioavailability, a wide dosage range, a linear dose-effect relationship, no need for constant monitoring of plasma concentrations. In comparison with old AEDs, the drug is better tolerated with long-term use.

In addition to epilepsy, topiramate can be successfully used for the prevention of migraine attacks. It seems promising to use the drug in the combined treatment of alcohol dependence, as well as some types of schizophrenia.Further research should clarify new possible indications for the use of topiramate.

Literature

1. Hauser W.A., Annegers J.F., Kurland K.T. et al. The prevalence of epilepsy in Rochester, Minnesota, 1940-1980 // Epilepsia. 1991; 32: 429-445.
2. Shorvon S.D. Epidemiology, classification, natural history, and genetics of epilepsy // Lancet. 1990; 336: 93–96.
3. Kwan P., Brodie M.J. Early identification of refractory epilepsy // N Engl J Med.2000; 342: 314-319.
4. MoshO S.L. Mechanisms of action of anticonvulsant agents // Neurology. 2000; 55: Suppl 1: S32-S40.
5. Tidwell A., Swims M. Review of the newer antiepileptic drugs // Am J Manag Care. 2003 Mar; 9: 3: 253-76; quiz 277-9.
6. Bergey G.K. Evidence-based treatment of idiopathic generalized epilepsies with new antiepileptic drugs // Epilepsia. 2005; 46: Suppl 9: 161-8.
7. Beghi E. Efficacy and tolerability of the new antiepileptic drugs: comparison of two recent guidelines // Lancet Neurol.2004 Oct; 3: 10: 618-21.
8. Faught E., Wilder B.J., Ramsay R.E. et al. Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 200-, 400-, and 600-mg daily dosages. Topiramate YD Study Group // Neurology. 1996 Jun; 46: 6: 1684–90.
9. Privitera M., Fincham R., Penry J. et al. Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 600-, 800-, and 1,000-mg daily dosages. Topiramate YE Study Group // Neurology. 1996 Jun; 46: 6: 1678–83.
10. Jette N., Hemming K., Hutton J.L., Marson A.G. Topiramate add-on for drug-resistant partial epilepsy // Cochrane Database Syst Rev. 2008 Jul; 16: 3: CD001417.
11. Ben-Menachem E., Sander J. W., Stefan H. et al. Topiramate monotherapy in the treatment of newly or recently diagnosed epilepsy // Clin Ther. 2008 Jul; 30: 7: 1180–95.
12. Schreiner A., ​​Stollhoff K., Ossig W. et al. Conversion from valproic acid onto topiramate in adolescents and adults with epilepsy // Acta Neurol Scand.2008 Dec; 26.
13. Sachdeo R. C., Glauser T. A., Ritter F. et al. A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL Study Group // Neurology. 1999 Jun; 10: 52: 9: 1882-7.
14. Freitag F. G., Forde G., Neto W. et al. Analysis of pooled data from two pivotal controlled trials on the efficacy of topiramate in the prevention of migraine // J Am Osteopath Assoc. 2007 Jul; 107: 7: 251-8.
15. Dahlof C., Loder E., Diamond M. et al. The impact of migraine prevention on daily activities: a longitudinal and responder analysis from three topiramate placebo-controlled clinical trials // Health Qual Life Outcomes.2007 Oct; 4: 5:56.
16. Afshar H., Roohafza H., Mousavi G. et al. Topiramate add-on treatment in schizophrenia: a randomized, double-blind, placebo-controlled clinical trial // J Psychopharmacol. 2008 May; 30.
17. Johnson B.A., Rosenthal N., Capece J.A. et al. Topiramate for treating alcohol dependence: a randomized controlled trial // JAMA. 2007 Oct; 10: 298: 14: 1641-51.
18. Olmsted C.L., Kockler D.R. Topiramate for alcohol dependence // Ann Pharmacother. 2008 Oct; 42: 10: 1475–80.
19. LaRoche S.M., Helmers S.L. The new antiepileptic drugs: scientific review // JAMA. 2004 Feb; 4: 291: 5: 605-14.
20. Doose D. R., Wang S. S., Padmanabhan M. et al. Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects // Epilepsia. 2003 Apr; 44: 4: 540-9.
21. Topamax [package insert]. Raritan, NJ: Ortho-McNeil; May 2002.

Topamax for weight loss: safety and effectiveness | SingleCare – Product Information

Product Information

Topamax is a brand name for a generic drug called topiramate.It is technically classified as an anticonvulsant that is used to treat conditions such as epilepsy, but is also used to treat other conditions such as migraines and bipolar disorder. Topamax is great for treating these conditions, but many people taking it will experience weight loss as a major side effect. Let’s take a closer look at how safe and effective Topamax is and how it affects weight loss.

Topamax Slimming

Topamax is FDA approved for the treatment and prevention of epilepsy.migraines, but the prescription drug is also well known for causing weight loss. While weight loss may be a positive benefit of taking Topamax, the FDA has not approved it for weight loss alone.

Topamax causes weight loss because it affects the appetite. People who take it and have a decreased appetite may feel less hungry and eat less because of it. Studies have shown that Topamax can also speed up your metabolism, which means your body burns calories faster.

Clinical trials have shown that approximately 6% -17% people who take Topamax experience weight loss, and while many people may see this as an added benefit, losing too much weight is not good. “Most people will experience moderate weight loss from Topamax,” says Kuldeep Singh, MD, a weight loss surgeon based in Baltimore and director of the Maryland Bariatric Center at Mercy Medical Center. Losing weight quickly can be unhealthy – it may be time to see your doctor if you are taking Topamax and this is happening to you.Maintaining a healthy weight is important, and the best way to find out what target weight is best for you is to ask your doctor. A decrease in body weight below target due to Topamax will be another sign that it is time to speak with your doctor.

Is it safe to take Topamax for weight loss?

Sometimes Topamax may be prescribed off-label to help you lose weight. Off-labeling occurs when a doctor gives someone a prescription for an FDA-approved drug to treat a condition other than that of their patient.It is legal and common in the medical industry, with an estimated 1 in 5 prescriptions being misused.

A doctor may give someone a prescription for Topamax to help with weight loss or to treat eating disorders such as overeating and detoxification that lead to weight gain. In order to be prescribed any weight loss medication, including topamax, someone must have a body mass index (BMI) of 30 or higher, according to Dr. Singh.

Studies have shown that people taking Topamax for weight loss lose approximately 11 pounds compared to placebo groups if they take the drug for at least four months, and that the effect of Topamax for weight loss increases both with the duration of treatment and with dosage. Research has also shown that topiramate treatment can increase the likelihood of statistically significant weight loss by more than sixfold.

While Topamax can be very effective for weight loss, it is not safe for everyone.The following groups of people should talk to their doctor before taking Topamax because they may have an increased risk of serious side effects if they take it:

  • People with kidney disease
  • People with lung disease or breathing problems …
  • People with liver disease
  • People with vision problems such as glaucoma
  • People with depression
  • People with suicidal thoughts or behaviors
  • People with osteoporosis
  • People with metabolic ketoacidosis

Pregnant women may be safe to take Topical women if the benefits of taking the medicine outweigh the potential risks.It is unlikely that Topamax will or should be prescribed during pregnancy for weight loss purposes. Topamax can harm the fetus and cause birth defects in the oral cavity if taken by pregnant women, so it is prescribed with caution and only if medically necessary. It is also excreted in breast milk, but it is not known if it will have a negative effect on breastfeeding. Topamax can reduce the effectiveness of birth control pills, so it is important to discuss the use of non-hormonal methods of contraception with your doctor if you do not want to get pregnant while taking Topamax.

People who are not pregnant and do not have any of the conditions listed above can safely take Topamax, but they may still experience side effects from taking it. Some of the more common side effects of Topamax besides weight loss are:

  • Dizziness
  • Fatigue
  • Numbness
  • Diarrhea
  • Loss of appetite
  • Loss of coordination
  • Paresthesia (burning)

Although this is rare, Topamax can cause more serious side effects that may require medical attention, such as confusion, memory problems, trouble concentrating, and speech problems.Some people will also experience mental health side effects such as depression, panic attacks, mood changes, and suicidal thoughts or behavior. If you have any of these symptoms, you should seek medical attention as soon as possible.

Another rare side effect of Topamax is vision problems that can lead to vision changes and blindness, which is why it is so important to call your doctor if your vision starts to change. This list of side effects is not all inclusive; If you need a complete list of Topamax side effects, ask your doctor or pharmacist for a medication guide.

If Topamax causes too many side effects, know you have other options. Topamax’s active ingredient, topiramate, is also the main ingredient in a slimming drug. Qsymia, which is a combination containing phentermine. According to Dr. Singh, Qsymia is one of the best medicines for long-term use in conjunction with diet and lifestyle changes for weight loss, especially for obese patients with class 1 or 2 obesity. Therefore, if you are unable to take Topamax due to an underlying health problem or because you are experiencing too many side effects, you can try asking your healthcare professional about Qsymia or other weight loss methods.

How to take Topamax to lose weight

Topamax can be taken to promote weight loss and control overeating and detoxification, but it is important to remember that it is not a substitute for visiting your doctor and drawing up a comprehensive weight loss plan. If you are interested in taking Topamax, it is best to make an appointment with your doctor to see if it is right for you. Your doctor will do a complete physical exam and ask about your medical history. If you and your doctor decide that Topamax can safely help you lose weight, you can get a prescription for it.

OTC Nausea Medicine for Adults

If you do get a prescription from your doctor, it is important to know how to take Topamax to get the best results. The initial dose of Topamax for weight loss is a low dose of 25 mg per day, but this dosage can be increased on a case-by-case basis, based on the medical history of each person and how much weight he needs to lose.

In a study by Journal of Clinical Psychiatry, patients with bipolar disorder and schizophrenia who were given an average of 195 mg of topiramate per day lost about 22 pounds over time.This shows that the dosage range of Topamax can range from low to high, and that doctors can increase or decrease the amount of Topamax someone is taking, depending on their individual results over time.

It may take some time to see the results of losing weight from taking Topamax. Some people may not notice the difference until they have taken the drug for at least four months, while others may start losing weight in the first month of taking it.Weight loss results from topiramate have been proven to increase over time.

Topamax can be taken with or without food, usually at the same time every day. It should not be taken at the same time as certain other medicines due to the potential for drug interactions. Here is a list of medications that you should not take Topamax with:

  • Antiepileptic drugs
  • Carbonic anhydrase inhibitors
  • CNS depressants
  • Oral contraceptives
  • Hydrochlorothiazide (HCTZ)
  • Pioglitripine 9002 9002 9002 Etymithymitiamine 9002 Topamax should not be taken with alcohol because it can cause drowsiness, increase the risk of kidney stones and cause metabolic acidosis.Metabolic acidosis is a condition in which too much acid builds up in body fluids and can become life-threatening if left untreated. If you start experiencing rapid breathing, confusion, extreme fatigue, and a rapid heartbeat while taking Topamax, you should seek medical attention as soon as possible, as these are signs that you may have metabolic acidosis.

    Weight gain after Topamax

    When someone stops taking Topamax, it is possible they will gain weight over time, especially if they have not combined Topamax with healthy lifestyle changes.In an observational study conducted by the National Library of Medicine, discontinuing Topamax for at least six months showed a tendency to return to baseline weight. Thus, people are more likely to return to where they weighed before they started taking Topamax, but this may take a while.

    This return to baseline weight can occur because the body no longer experiences decreased appetite and accelerated metabolism. The best way to maintain weight after you stop taking Topamax is to make healthy lifestyle changes that will support you on your way to weight loss.

    5 Safe Ways to Lose Weight

    Topamax may be helpful on your weight loss journey if approved by your doctor, but it is not the only way to lose weight. Lifestyle changes can help you lose weight and keep it off so you can enjoy the weight loss benefits without taking Topamax, while taking or after taking it. Here are some of the safest ways to lose weight.

    1. Improve your eating habits.

    Healthy eating is one of the safest and best ways to lose weight.Being mindful of what and how much you eat will help you lose weight if you do it right. You should talk to your doctor for the best advice on what to eat to lose weight, but making some small changes, such as eating more fruits and vegetables, can be a great start.

    Processed foods, refined carbohydrates, sugar and alcohol are all examples of foods that can cause weight gain. Fresh fruits, vegetables, and high-quality proteins like salmon, beans, and eggs are all great examples of foods that the body can easily process and obtain vital nutrients from.

    2. Exercise regularly.

    According to the Centers for Disease Control and Prevention (CDC), exercise not only helps control weight, but it also lowers high blood pressure, lowers the risk of type 2 diabetes, and can even reduce symptoms of depression and anxiety. People differ in how much exercise they need to lose weight, so it is a good idea to talk to your doctor about how often you should exercise. Some great weight loss exercises include walking, cycling, swimming, and strength training.

    3. Reduce stress.

    Stress is associated with many health problems such as anxiety and depression. Feeling stressed can lead to emotional overeating, which over time can lead to weight gain. Finding ways to reduce stress can help you lose weight. You can do meditation, yoga, take a walk, or call a friend or family member. You can also ask your doctor or psychologist about proven stress reduction strategies that fit into your lifestyle.

    4. Get enough sleep.

    According to the Sleep Foundation, lack of sleep can increase appetite and lead to metabolic disorders. Getting enough sleep can help your body function normally and give you more energy for things like exercise to help you lose weight. Getting enough sleep can also reduce stress levels, which can help you control any urge to overeat.

    5. Try safe diet pills and supplements.

    There are countless diet pills and supplements on the market that are said to induce weight loss, such as Hydroxycut and glucomannan, but should not be used as a substitute for healthy lifestyle changes. When people go for weight loss drugs, most people do it because it’s easy to do, according to Dr. Singh. If someone seriously changes their lifestyle and eating habits first, they will indeed see significant improvement with Topamax or other weight loss medications.The mood is the most important thing. Medicines are not a substitute for proper diet and exercise.

    Topiramate for weight loss – reviews of real people

    Reviews

    Serious drug, suppresses appetite, but bad for the kidneys

    Topiramate does indeed reduce weight and has been shown to promote weight loss in certain types of obesity (due to overeating, nighttime intake, etc.).etc.). The drug acts on the brain in such a way that the addiction to food simply goes away and you start to eat only what you need.

    Thanks to these pills, I got a normal diet, the portion decreased by 2, and then even 3 times, and naturally I began to lose weight, despite the fact that I move a lot and the remaining extra pounds were simply “shaken”.

    But the medicine itself is intended for people with epilepsy and contains the active substance topiramate of synthetic origin.It has many contraindications. I also faced several, after which I decided to quit with such weight loss. I got sand in my kidneys, which caused pyelonephritis and prolonged pain. When I announced at the urologist’s appointment that I was taking Topiramate, he quarreled strongly, said to cancel the drug and never use it again. I also learned that it can cause kidney failure.

    2017.08.11 at 17:54 wrote:

    alfi

    Only under the supervision of a doctor

    The course of pills helped to really lose weight, but at the same time I had to follow a strict diet with a calorie deficit, constantly calculate the balance of BJU and eat small, strictly by the hour, small portions.There were great difficulties with the selection of the dosage. Since the pills are strong and have a lot of side effects, the doctor should make the appointment. Self-experimentation is fraught with serious health problems.

    In the first days of admission, constant nausea bothered, there were sensations as after motion sickness in transport, distraction of attention was observed. After about a week, the body adapted. Within 2 weeks she took Topiramate in a minimum dosage of 25 mg. As the body adapted and reacted normally, the dose was gradually increased to 100 mg.And only after that did the real weight loss begin. Active fat burning processes started. Both the subcutaneous and the dangerous visceral left. It is also impossible to just throw pills, you need to gradually reduce the dose. If everything is done correctly, then it will not be difficult to keep the results of weight loss. The tablets are very poorly combined with a large number of medications.

    2017.06.14 at 12:58 wrote:

    Sofi

    Not for weight loss

    Topiramate is an antieleptic drug, and weight loss when taken is considered as a side effect, and not as the main effect of the drug, the mechanism of fat burning during its use is not fully understood.The drug does not reduce appetite, pressure and heart rate does not increase, but a person still loses weight, even without denying himself “harmful” products, sometimes weight loss reaches 4 kg / week.

    You should not consider it as a means for losing weight, since the drug has an effect on the neurons of the brain, and, accordingly, weight loss is not the only side effect that threatens when taking it. The use of this remedy in childhood and adolescence is especially dangerous, in addition to dizziness and migraines, it can cause impaired speech, vision and personality disorder, hallucinations.These symptoms may appear as early as a month after starting the drug and are sometimes irreversible, even after discontinuation. Therefore, it is simply stupid for a healthy person to seriously think about the use of Topiramate for weight loss, and if he was nevertheless prescribed by a doctor, then constantly monitor the general condition of the body and internal organs, it is necessary to regularly take tests.

    2017.05.26 at 12:55 wrote:

    marmelad

    Serious side effects

    Took pills for 14 days (minimum therapeutic course).Topiramate has long been used in the treatment of obesity and pathological eating behavior, so there was no concern. Indeed, it turned out to be painless to give up sweets, to overcome psychological dependence on food. Strong positive or negative emotions were no longer seized. She did not reward herself for her successes with something tasty. Beginning with a minimum dose of 25 mg, increasing gradually. The body must adapt. It is imperative to test the minimum dose, since the drug has a lot of side effects.I immediately began to feel dizzy in the morning, I was tormented by sleepiness all day, my attention was disturbed and my thinking slowed down. It became impossible to drive a car. I thought that in a few days it would pass, but the symptoms accompanied me all 2 weeks.

    I did not lose much weight, I lost only 2 kg. A plus I can say is that the pills are approved for admission for diabetes mellitus. They quickly lower blood sugar levels, there are no bouts of hunger. It immediately became easier to control appetite.The drug is prohibited for liver and kidney problems.

    2017.03.16 at 11:19 wrote:

    sempepera

    PHARMATEKA »New drugs for the treatment of obesity

    Two new drugs for the treatment of obesity entered the US pharmaceutical market – Belvik (lorcaserin, Eisai / Arena Pharmaceuticals) and Ximia * (combination of phentermine and topiramate with controlled release of active ingredient, Vivus).Both drugs were approved for medical use a year ago (in June and July 2012) and became the first drugs (drugs) registered in the country for the last 13 years for long-term obesity therapy [1]. The registration of lorcaserin and the combination of fenteramine with topiramate was ranked by Nature magazine as one of the most significant advances in the field of pharmacy in 2012 [2], due to the widespread prevalence of obesity, its clinical, social and economic consequences, as well as the lack of drugs with a good benefit / risk for its treatment.Despite numerous attempts to develop effective drugs for the treatment of obesity, most of them were either not approved for use for this indication, or were withdrawn from the market due to serious adverse reactions (see table). After the withdrawal of sibutramine, the only drug approved for long-term use by obese patients was orlistat, also not devoid of serious drawbacks (low efficiency, gastrointestinal side effects, rare cases of hepatotoxicity) [3, 4].

    Lorcaserin and the phentermine / topiramate combination were not approved by the FDA on the first try.In 2010, the FDA assessed the benefit / risk ratio of lorcaserin as unfavorable due to its lack of efficacy in clinical trials and an increased risk of developing certain tumors (breast adenocarcinomas in females and cerebral astrocytomas in males) observed in experiments in rats, and risk of developing valvulopathies, mental, cognitive and serotonergic side effects [6].

    According to FDA standards, a drug for the treatment of obesity should reduce body weight within a year by at least 5% compared to placebo, and the number of patients who achieve 5% weight loss should be at least 2 times higher than in placebo group [3].Lorcaserin did not meet the first criterion – the average weight loss with its use was 5.8% compared to 2.5% in the placebo group, i.e. the difference between the groups (3.3%) did not reach the required level. However, he met another criterion – the number of patients whose body weight decreased by at least 5% after 1 year of treatment was 47% in the active drug group compared to 22% in the placebo group [8]. In a letter to the manufacturer, the FDA defined the drug’s clinical efficacy as “minimal” [9].After refusing to register the drug in 2010, the FDA recommended that the manufacturer submit the final report of the BLOOM-DM (Behavioral modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus) study [10].

    The results of this study, as well as careful analysis of other clinical and experimental data by independent experts, showed that the use of lorcaserin can achieve clinically significant weight loss that meets the requirements of US regulatory authorities, and was associated with a number of other beneficial effects on cardiometabolic and anthropometric parameters, in T.including on blood pressure, LDL cholesterol, waist volume and glycated hemoglobin in patients with diabetes mellitus [6, 8]. It was also shown that mammary tumors detected in animals were significantly more likely to be benign than previously assumed [6]. Concentrations of the drug in the central nervous system in humans were low [11], which suggested a low probability of developing brain tumors in humans [5]. The results of in vitro studies indicated that, at the recommended therapeutic doses, the effect of lorcaserin on 5-HT2B receptors, the stimulation of which can lead to the development of pulmonary hypertension and valvulopathy, is unlikely [11].In clinical trials, an insignificantly increased risk of valvulopathy was observed in only one of the three phase III studies (2.9% at the end of week 52 when used at a dose of 10 mg 2 r / day versus 0.5% in the placebo group, p = 0.122) [ten]. Based on the analysis of pooled data from three studies (n = 5249), the incidence of valvulopathy was not significantly different between the lorcaserin and placebo groups [12]. The risk ratio of developing valvulopathy with the use of lorcaserin in different doses ranged from 1.03 to 1.16 and, at least in part, could be associated with a more pronounced decrease in body weight in the active drug group.

    Based on data from repeated analyzes, the FDA concluded that the benefits of using lorcaserin outweigh the risks, and, along with diet and physical activity, recommended it for long-term weight control in adults with a body mass index (BMI) of 30 kg / m2 or more, and persons with a BMI of 27 kg / m2 who have at least one of the conditions associated with increased weight – diabetes mellitus, arterial hypertension or dyslipidemia. It should be noted that the results of the FDA Advisory Panel vote on re-consideration of the application for registration of lorcaserin were not unanimous (18 in favor, 4 against) – mainly due to concerns about cardiovascular risk.

    The drug is assigned category IV in the classification of controlled substances by the US Drug Enforcement Agency (rather low potential for the development of addiction). This is due to the fact that stimulation of 5-HT2A receptors can lead to the development of hallucinogenic effects and euphoria, which was observed in isolated cases with the use of lorcaserin [13]. In the FDA’s safety classification for use during pregnancy, it is assigned to category X (fetal developmental disorders have been identified or there is evidence of a risk of negative effects of this drug on the human fetus, the use is absolutely contraindicated – there are no situations where the benefit to the mother would exceed the risk to the fetus) [14 ].In order to increase the safety of the drug in real medical practice, the FDA obliged the manufacturer to develop a REMS (Risk Evaluation and Mitigation Strategies) strategy aimed at identifying risks in the post-registration period and introducing adequate measures to minimize their consequences.

    Approximately the same path to registration in the United States had to be overcome by combinations of phentermine and topiramate. When considering the first application, the FDA refused to register it for safety reasons, despite strong evidence of efficacy (average weight loss over the course of a year – about 10%) [15].In particular, the concerns of the members of the Advisory Commission caused adverse events from the cardiovascular system, especially increased heart rate at rest, as well as mental disorders, including suicidal thoughts, cognitive disorders, including memory impairments, congenital anomalies and metabolic acidosis. [3]. The FDA did not require the manufacturer to conduct new studies, but did request additional information to more accurately assess the risks [16]. After reconsidering the submissions, the Advisory Commission, by an overwhelming majority (20 to 2), recommended approval of the combination of phentermine and topiramate under the new trade name Ximia for the same indications as lorcaserin, with a number of caveats.In particular, the instructions for medical use of Xymia emphasize that its effect on cardiovascular morbidity and mortality has not been established. Phentermine / topiramate is not recommended for patients with unstable angina pectoris and cerebrovascular disease; when using it, it is necessary to monitor the heart rate [5].

    The drug is classified in category X according to the classification of safety for use during pregnancy. This is associated with an increased risk of teratogenicity (mainly orofacial clefts), identified with the use of topiramate as monotherapy in patients with epilepsy [17].Ximia can also cause metabolic acidosis, negatively affecting oxygenation and fetal development, and thus increase the risk of other adverse pregnancy outcomes, including intrauterine death. In addition, phentermine is classified as a controlled substance: in the classification of the US Drug Enforcement Administration, it belongs to category III, that is, the risk of developing dependence with its use is estimated to be higher than with the use of lorcaserin. To assess and minimize all risks associated with the use of Xymia, the manufacturer has developed a REMS strategy.

    In Europe, where regulatory requirements for obesity drug registration are more stringent than in the United States (10% weight loss from baseline to be maintained for 1 year and 5% higher than placebo ) [15], both new obesity drugs were denied registration. The manufacturer of lorcaserin withdrew the application for registration of the drug in Europe, citing as a reason the impossibility of resolving issues related to these experimental studies with the regulatory agency within the time frame of the registration process [18].

    However, it is possible that the main reason for refusal of registration in the European Union is the moderate efficacy of the drug, which does not meet the EMA criteria. As for the combination of phentermine with topiramate, the EMA twice refused its registration, demanding from the manufacturer to conduct additional studies to study its safety on the part of the cardiovascular system and the central nervous system in long-term use [19].

    Pharmacological properties and results of clinical trials of lorcaserin

    Lorcaserin is a potent agonist of 5-hydroxytryptamine (serotonin) receptors with a selective effect on 5-HT2C receptors located mainly in the central nervous system, incl.hours in the hypothalamus. The latter are thought to play a major role in serotonergic appetite control [20]. Stimulation of 5-HT2C receptors in the hypothalamus leads to the elimination of hunger and the rapid appearance of a feeling of fullness even after eating a small amount of food. At the same time, the affinity of the drug for other serotoninergic receptors 5-HT2A and 5-HT2B, respectively, is 15 and 100 times lower than for 5-HT2C receptors [11].

    The efficacy and safety of lorcaserin were studied in three large multicenter phase III clinical trials – BLOOM ((Behavioral Modification and Lorcaserin for Overweight and Obesity Management) (n = 3800) [21], BLOSSOM (Behavioral modification and Lorcaserin Second Study for Obesity Management) (n = 4008) [22] and BLOOM-DM (Behavioral Modification and Lorcaserin for Obesity and Overweight Management in Diabetes Mellitus) (n = 604) [10].In the first two, the drug was studied on persons with increased body weight or obesity without complications (so-called healthy), in the third – in patients with increased body weight / obesity and diabetes mellitus. By the end of the 52nd week of lorcaserin use, the decrease in body weight in relation to placebo was 3.6 kg in the first study (3.6% of body weight) in “healthy” individuals [21], in the second – 2.9 kg [22] , in patients with diabetes mellitus – 3.1 kg [10]. A 5% decrease in body weight was correspondingly achieved in 27.2%; 22.2% and 21.4% of participants taking the active drug.According to the results of a meta-analysis of randomized controlled trials of the drug lasting a year, the average decrease in body weight under its influence in relation to placebo was 3.23 kg, and the decrease in BMI was 1.16 kg / m² [23].

    With the use of lorcaserin for 8 and 12 weeks, the corresponding indicators of body weight loss were 1.6 and 2.9 kg. Thus, the results obtained did not differ significantly from the results of the study of the nonselective agonist of serotonin receptors dexfenfluramine [24], and the assumption that the selective effect on 5-HT2C receptors would contribute to a more pronounced effect on weight was not confirmed [15].Lorcaserin reduced body weight to a lesser extent than the withdrawn from the market rimonabant [25-27] or sibutramine [28, 29].

    In phase III clinical trials, weight loss of at least 5% was achieved only by 45% of participants who received lorcaserin [30]. However, its use was associated with other beneficial effects – a decrease in waist volume, a decrease in blood pressure, total cholesterol, LDL cholesterol, triglycerides and glycated hemoglobin in patients with diabetes mellitus [10, 23].

    Lorcaserin was generally well tolerated. The main reason for dropping out of studies (45–50% of patients) was lack of efficacy rather than problems with tolerance [31]. In clinical trials, lorcaserin was more likely to cause headache, nausea and dizziness than placebo, less often diarrhea [23]. The use of lorcaserin was associated with an increased risk of acute visual impairment, mild depressive and cognitive disorders, including memory impairment [21, 22]. With the simultaneous use of lorcaserin with other serotoninergic or antidopaminergic drugs, there is a risk of developing serotonin syndrome [32].Lorcaserin is contraindicated in pregnant women and women planning pregnancy, as well as breastfeeding mothers.

    The drug is recommended to be discontinued in patients who fail to achieve a 5% decrease in body weight in the first 12 weeks of treatment, since clinical studies have shown that in this case the probability of achieving an effect with longer therapy is extremely low [31].

    Pharmacological properties and results of clinical studies of the combination of phentermine with topiramate

    The components of the phentermine / topiramate combination have long been used in medical practice for weight loss.Sympathomimetic phentermine is officially approved in the United States only for short-term (up to 12 weeks) use, since its efficacy and safety with long-term use have not been studied. The use of the antiepileptic drug topiramate for this indication is off-label, although its ability to reduce body weight has been shown in randomized controlled trials. According to the results of a meta-analysis of these studies, it significantly reduces body weight by an average of 3.95 kg [33].The exact mechanism of action of topiramate leading to weight loss is not known. It is assumed that it is mediated through the blockade of voltage-gated sodium channels, glutamate receptors and mitochondrial carbonic anhydrase, and an increase in GABA activity [34]. The combination of phentermine with topiramate causes appetite suppression and enhances satiety [30]. It is possible that the drug also increases energy expenditure, which was shown in experiments on animals [35].

    The combination is intended for oral administration once a day.In clinical trials, it has been studied in three doses – 3.75 mg phentermine / 23 mg topiramate (low dose), 7.5 / 46 mg (medium dose) and 15/92 mg (full dose), respectively.

    In a 6-month phase II study, a synergistic effect of the combination components was demonstrated, 42% of patients achieved a weight loss of more than 10% compared with placebo [23]. When compared with the results of clinical trials of other drugs, phentermine / topiramate was superior in efficacy to orlistat, sibutramine and rimonabant [25, 27, 36, 37], as well as lorcaserin [38].

    In three large phase III clinical trials involving a total of more than 4500 obese adults, including those with concomitant diseases (type 2 diabetes mellitus, hypertension, dyslipidemia), a decrease in body weight of at least 5% in relation to placebo was achieved in approximately 75% of participants receiving phentermine / topiramate [30]. By the end of the 56th week of treatment, the average weight loss was 10.6%, 8.4, and 5.1% when using doses of 15/92 mg, 7.5 / 46 and 3.75 / 23 mg, respectively, compared with 2.5% in the placebo group (p <0.0001) [38].Participants who received the active drug in medium and full doses showed a decrease in systolic pressure, fasting triglyceride and insulin levels, and an increase in HDL cholesterol compared with the placebo group [3]. A decrease in total cholesterol and LDL cholesterol, as well as in diastolic blood pressure, was observed only in the subgroup receiving phentermine / topiramate at a dose of 15/92 mg. The beneficial effect of the drug on body weight persisted for at least two years [39].

    Among the adverse events registered in clinical studies, the prevailing effects typical for the components of the combination – dry mouth, constipation, insomnia, palpitations, dizziness, paresthesia, impaired attention in combination with headache, taste disturbance, alopecia and hypokalemia.Of these, paresthesias, dizziness, taste disturbances, insomnia, constipation and dry mouth occurred with a frequency of more than 5% [38]. The drug can provoke acute visual impairment and angle-closure glaucoma. The development of symptoms of depression, suicidal thoughts and impaired cognitive functions is possible, especially at the beginning of treatment. As well as lorcaserin, phentermine / topiramate is contraindicated in pregnant and breastfeeding women, and women of reproductive age are advised to use reliable contraception during treatment.

    Thus, two new drugs for the treatment of obesity have appeared on the US market. One of them, phentermine / topiramate, appears to be more effective than all other drugs used to treat obesity, but its effectiveness, as well as the overall effectiveness of pharmacotherapy in this condition, is estimated by experts as moderate [38]. The second drug, lorcaserin, appears to be less effective than phentermine / topiramate, but superior in tolerability [40]. Since indirect comparison of results from clinical trials is difficult and incorrect, this must be proven in direct comparative studies.In addition, both drugs raise safety concerns, especially with long-term use.

    Significant disadvantages of both drugs include their adverse effect on the fetus, requiring special training for women of childbearing age – a significant part of drug users for the treatment of obesity [23]. Whether new drugs will be able to make a significant contribution to the treatment of obesity and the prevention of its complications will be shown by new clinical and pharmacoepidemiological studies, incl.including programs to identify and minimize risks, carried out by their manufacturers.

    1. Rueda-Clausen CF, Padwal RS, Sharma AM. New pharmacological approaches for obesity management. Nat Rev Endocrinol 2013; 9 (8): 467-78.
    2. Heuer RD, Rosenzweig C, Steltzner A, et al. 366 days: Nature’s 10. Nature 2012; 492 (7429): 335–43.
    3. Shin JH, Gadde KM. Clinical utility of phentermine / topiramate (Qsymia ™) combination for the treatment of obesity.Diabetes Metab Syndr Obes 2013; 6: 131–99.
    4. Morris M, Lane P, Lee K, Parks D. An integrated analysis of liver safety data from orlistat clinical trials. Obes Facts 2012; 5 (4): 485–94.
    5. Cheung BMY, Cheung TT. Safety of Antiobesity Drugs. Ther Adv Drug Safe 2013; 4 (4): 171–81.
    6. Colman E, Golden J, Roberts M, et al. The FDA’s assessment of two drugs for chronic weight management. N Engl J Med 2012; 367 (17): 1577-79.
    7. Kang JG, Park CY.Anti-Obesity Drugs: A Review about Their Effects and Safety. Diabetes Metab J 2012; 36 (1): 13-25.
    8. Nigro SC, Luon D, Baker WL. Lorcaserin: a novel serotonin 2C agonist for the treatment of obesity. Curr Med Res Opin 2013; 29 (7): 839-48.
    9. Arena Pharmaceuticals Press Releases, 2010. http://invest.arenapharm.com/releases.cfm.
    10. O’Neil PM, Smith SR, Weissman NJ, et al. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study.Obesity (Silver Spring) 2012; 20 (7): 1426–36.
    11. Thomsen WJ, Grottick AJ, Menzaghi F, et al. Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization. J Pharmacol Exp Ther 2008; 325 (2): 577-87.
    12. Weissman NJ, Sanchez M, Koch GG, et al. Echocardiographic assessment of cardiac valvular regurgitation with lorcaserin from analysis of 3 phase 3 clinical trials. Circ Cardiovasc Imaging 2013; 6 (4): 560–67.
    13. Shram MJ, Schoedel KA, Bartlett C, et al.Abuse potential assessment of lorcaserin, a selective and potent agonist at the serotonin2C (5-HT2C) receptor, in healthy male and female recreational polydrug users. Clin Pharmacol Ther 2010; 87: S1.
    14. Kang JG, Park CY. Anti-Obesity Drugs: A Review about Their Effects and Safety. Diabetes Metab J 2012; 36 (1): 13-25.
    15. Heal DJ, Gosden J, Smith SL. What is the prognosis for new centrally-acting anti-obesity drugs? Neuropharmacology. 2012; 63 (1): 132–46.
    16. VI-0521 (QNEXA®) ADVISORY COMMITTEE BRIEFING DOCUMENT.NDA 022580 Endocrinologic and Metabolic Drugs Advisory Committee Meeting July 15, 2010 http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM218821.pdf
    17. Aunt, Russell et al. … Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 2008; 71 (4): 272–76.
    18. Lisa Nainggolan. New Obesity Drug, Belviq, in US Pharmacies Next Week.Medscape. Jun 07, 2013.
    19. Refusal of the marketing authorization for Qsiva (phentermine / topiramate) EMA / 666052/2012. www.ema.europa.eu/docs/en_GB/document_library/…/WC500134085.pdf
    20. Lam DD, Przydzial MJ, Ridley SH, et al. Serotonin 5-HT2C receptor agonist promotes hypophagia via downstream activation of melanocortin 4 receptors. Endocrinology 2008; 149: 1323-28.
    21. Smith SR, Weissman NJ, Anderson CM, et al. Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) Study Group.Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 2010; 363: 245-56.
    22. Fidler MC, Sanchez M, Raether B, et al; BLOSSOM Clinical Trial Group. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab 2011; 96: 3067-77.
    23. Chan EW, He Y, Chui CS, Wong AY, et al. Efficacy and safety of lorcaserin in obese adults: a meta-analysis of 1-year randomized controlled trials (RCTs) and narrative review on short-term RCTs.Obes Rev 2013; 14 (5): 383–92.
    24. Guy-Grand B, Apfelbaum M, Crepaldi G, et al. International trial of long-term dexfenfluramine in obesity. Lancet 1989; 2: 1142–45.
    25. Van Gaal LF, Rissanen AM, Scheen AJ, et al. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 2005; 365: 1389–97.
    26. Scheen AJ, Finer N, Hollander P, et al.Efficacy and tolerability of rimonabant in overweight or obese patients with Type 2 diabetes: a randomized controlled study. Lancet 2006; 368: 1660–72.
    27. Pi-Sunyer FX, Aronne LJ, Heshmati HM, et al. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. J Am Med Assoc 2006; 295: 761-75.
    28. Apfelbaum M, Vague P, Ziegler, O, et al. Long-term maintenance of weight loss after a very-low-calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine.Am J Med 1999; 106: 179-84.
    29. James WP, Astrup A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomized trial. STORM study group. Sibutramine trial of obesity reduction and maintenance. Lancet 2000; 356: 2119-25.
    30. Fleming JW, McClendon KS, Riche DM. New obesity agents: lorcaserin and phentermine / topiramate. Ann Pharmacother 2013; 47 (7-8): 1007-16.
    31. Gallwitz B. Novel Oral Anti-Obesity Agents: New Perspectives with Lorcaserin? Drugs 2013; 73: 393–95.
    32. Eisai Inc. Belviq (lorcaserin hydrochloride) tablets, for oral use. 2012.http: //www.accessdata.fda.gov/drugsatfda_docs/label/2012/022529lbl.pdf.
    33. Fiedorowicz JG, Miller DD, Bishop JR, ​​et al. Systematic Review and Meta-analysis of Pharmacological Interventions for Weight Gain from Antipsychotics and Mood Stabilizers. Curr Psychiatry Rev 2012; 8 (1): 25–36.
    34. Antel J, Hebebrand J. Weight-reducing side effects of the antiepileptic agents topiramate and zonisamide.Handb Exp Pharmacol 2012; (209): 433-66.
    35. Richard D, Ferland J, Lalonde J, et al. Influence of topiramate in the regulation of energy balance. Nutrition 2000; 16 (10): 961-66.
    36. Van Gaal LF, Broom JI, Enzi G, Toplak H. Efficacy and tolerability of orlistat in the treatment of obesity: a 6-month dose-ranging study. Orlistat dose ranging study group. Eur J Clin Pharmacol 1999; 54: 125-32.
    37. Déspres JP, Golay A, Sjöström L. Rimonabant. In: Obesity Lipids Study Group (Ed.), Effects of Rimonabant on Metabolic Risk Factors in Overweight Patients with Dyslipidemia. N Engl J Med 2005; 353: 2121-34.
    38. Smith SM, Meyer M, Trinkley KE. Phentermine / topiramate for the treatment of obesity.