Sibutramine: what is dangerous, mechanism of action, how to take, consequences

Rapid weight loss without any effort sounds very tempting to many who are tired of extra pounds. That is why “magic” weight loss drugs are in demand, and will probably always be in demand, among a part of the predominantly female population who are unhappy with their weight.

Sibutramine hydrochloride monohydrate, discovered by the international corporation Abbott Laboratories at the turn of the last decade of the last century and not having justified its first purpose as an antidepressant, turned out to be a pronounced anorectic. The effect of this substance in terms of suppressing the feeling of hunger turned out to be unexpectedly effective, and the loss of excess kilograms was so significant that it began to be used as a drug for obesity since 1997, prescribing it to patients with excess weight caused by uncontrolled food intake.

Why is sibutramine banned?

The fame of Sibutramine as an effective fat burner, which also eliminates the desire to snack, quickly spread across countries and continents, since the problem of excess weight is quite acute not only in the United States, but also in most economically developed countries of Europe. The World Health Organization considers this problem an epidemic and, naturally, the appearance of a new drug that eliminates the feeling of hunger and stimulates metabolic processes in the body was perceived more than favorably. Sibutramine and drugs containing it began to be prescribed to patients with excess weight left and right.

However, reports of mental disorders in patients taking drugs with this active ingredient began to appear quite quickly. Among them, cases of suicide, acute cardiovascular pathologies with a fatal outcome, especially among the elderly, have become more frequent. In addition, drugs with Sibutramine can, according to some data, cause a drug-like addiction. All these facts and a long list of side effects that were discovered during more thorough studies of the properties of this drug, explain why Sibutramine is banned. Since 2010, the sale of drugs with this active ingredient has been temporarily suspended in the European Union, Australia, the USA, Canada and Ukraine; in Russia, they can only be purchased with a doctor's prescription.

Indications for use of this drug are primary food obesity of II-III degree, when the body mass index exceeds 30-35 kg/m² with the ineffectiveness of other treatment methods. Both immediately after its appearance and at present, this drug for extra pounds was not recommended for everyone, but in especially severe cases of obesity. The treatment regimen for Sibutramine involves a low-calorie diet and exercise. It is also prescribed to people suffering from insulin-independent diabetes, hyper- or hypoproteinemia. In this case, the recommended patient body mass index is 27 kg/m² and above.

Complex therapy, including medications with Sibutramine, is carried out under the supervision of a specialist with practical experience in treating excess weight. An important part of it is the formation of the patient's psychological readiness to change their habits in terms of diet and nutrition, as well as to changes in lifestyle, and maintaining them after discontinuing drug treatment.

Pharmacodynamics

The mechanism of action of this substance is that it promotes rapid satisfaction of hunger, activating the feeling of satiety and, thus, reducing the amount of food consumed without any effort on the part of the patient.

The beginning of the transmission of chemical signals (for example, about satiety during food intake) between neurons of the brain is the release of neurotransmitters, serotonin and norepinephrine, into the intercellular space (synapse), where the signal is received. Sibutramine molecules block the return of neurotransmitters back to the presynaptic cell. Due to this, the concentration of serotonin and norepinephrine in the synapse increases, potentiating the stimulation of the neuron receiving the impulse. The signal about satiety enters the postsynaptic cells more intensively, the body does not require the intake of large amounts of food. In addition, the drug increases the production of heat by the body, forcing metabolic processes and forming monodemethyl- and didemethylsibutramine - active metabolites that can themselves inhibit the reuptake of released neurotransmitters (serotonin and norepinephrine), as well as the pleasure hormone dopamine, but to a much lesser extent. By acting in this way, Sibutramine promotes a rapid emergence of a feeling of satiety, and it becomes permanent. The desire to snack disappears by itself, food consumption is significantly reduced, which leads to rapid weight loss.

The active substance and its active metabolites are indifferent to the release of the enzyme monoamine oxidase and its activation, do not interact with neurotransmitters, including catecholamines, serotonin, histamine, acetylcholine, glutamic acid and benzodiazepines. They suppress the capture of membrane serotonin receptors by platelets and can change their functions.

The reduction of fat deposits with the help of these medications is accompanied by an increase in the level of high-density lipoproteins (“good” cholesterol) in the blood plasma against the background of a quantitative reduction in triacylglycerides, total cholesterol at the expense of “bad” cholesterol and uric acid.

During treatment with these medications, cases of minor increases in blood pressure and heart rate were mainly recorded, but more serious changes in these parameters also occurred. Most medications with sibutramine are monodrugs, however, in addition to the main active ingredient, Reduksin also contains microcrystalline cellulose, a natural non-food product that has no side effects. It has the property of lingering in the stomach, swelling under the influence of liquid, thus providing a feeling of satiety. In combination with sibutramine, it complements its effect. It is able to absorb not only water, but also putrefactive bacteria, cleanses the intestines well and prevents food poisoning.

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Pharmacokinetics

When taken orally, the active component is rapidly absorbed from the gastrointestinal tract (about 80%). Getting into the liver, Sibutramine is metabolized into monodemethyl- and didemethylsibutramine. After 72 minutes from taking the drug, dosed at 0.015 g, the highest concentration of the active ingredient is observed, and from three to four hours - its metabolites. Taking the capsule with food, the patient reduces the maximum concentration of metabolites by a third, and the time to achieve it increases by three hours, without changing the total concentration and distribution. Sibutramine (almost completely) and its metabolites (> 90%) bind to serum albumins and spread at a good rate in the tissues of the body. The concentration of active substances in the serum reaches a state of equilibrium after four days from the start of therapy and is twice their serum concentration determined after the first dose.

Inactive demethylated metabolites are excreted mainly in urine, less than 1% is excreted in feces. The half-life of sibutramine is 66 minutes, its metabolites (monodesmethyl- and didesmethylsibutramine) - 14 and 16 hours, respectively.

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Dosing and administration

The drug is taken once in the morning, regardless of food intake. Treatment begins with one capsule of 0.01 g, which is swallowed whole and washed down with water in sufficient quantity. If the weight loss is less than two kilograms during the first four weeks of therapy and good tolerability, a higher daily dosage of 0.015 g is prescribed. If in the next four weeks the weight decreases by less than two kilograms, the drug is discontinued as ineffective in this case, since higher dosages are not recommended.

Treatment is stopped in the following cases:

• when the patient loses less than 5% of their initial weight over three months;
• when weight loss has stabilized at less than 5% of the initial weight;
• when, after already achieving weight loss, the patient again gains three kilograms or more.

Treatment with this drug is possible for no more than two years.

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Use Sibutramine during pregnancy

The results of Sibutramine tests on laboratory animals indicate that this active substance does not affect the ability to fertilize, however, the teratogenic effect of sibutramine on the fetus was observed in the offspring of laboratory rabbits. They were found to have physical anomalies related to appearance, as well as skeletal structure.

Medicines containing Sibutramine are prohibited for use by pregnant and lactating women. Throughout the entire course of treatment and for one and a half months after the end of treatment with these drugs, female patients of fertile age must use reliable contraception.

Contraindications

• age restrictions: not prescribed to minors and persons over 65 years of age;
• secondary obesity caused by diseases of the endocrine and central nervous systems, and other organic causes;
• eating disorders – bulimia, anorexia (present or in history);
• mental pathologies;
• generalized tic;
• circulatory disorders in parts of the brain (present or in history);
• toxic goiter;
• ischemic heart disease (present or in history), heart rhythm and heart rate disturbances, chronic decompensated dysfunction of the heart muscle;
• circulatory disorders in peripheral vessels;
• uncontrolled increase in blood pressure above 145 mm Hg;
• severe degrees of liver and/or kidney dysfunction;
• prostate adenoma with urinary retention;
• pheochromocytoma
• substance abuse and/or alcoholism;
• angle-closure glaucoma;
• hypolactasia, glucose-galactose malabsorption syndrome;
• known sensitization to sibutramine and/or other ingredients of the drug.

It should be prescribed with special caution to patients with a history of hypertension, circulatory disorders, muscle spasms, coronary insufficiency, epilepsy, liver and/or kidney dysfunction, gallstone disease, glaucoma, hemorrhages, tics, and also to those taking medications that impair blood clotting.

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Side effects Sibutramine

This substance is a very effective anorectic, and, naturally, those who want to lose weight and have read the rave reviews, of which there are many, have a question: What is the danger of Sibutramine?

Of course, like any substance, it can cause an allergy. In most cases, it is not anaphylactic shock, but a more harmless reaction of the body, for example, a rash from Sibutramine. Unpleasant, but not dangerous. Stop taking it - it will itch and go away.

A more serious consequence is addiction. This drug is not recommended for use for more than a year, but people who start taking it often cannot stop, they develop a real drug addiction, which is essentially a subspecies of drug addiction. Not everyone. However, who can guarantee that their body will be resistant to this property of this drug?

There will be no real narcotic high from Sibutramine, but when you stop taking it, which is recommended to do gradually, you may experience sensations similar to "withdrawal". This happens even with a short-term, three months, intake of the drug. This is dizziness and migraines, sleep disorders and anxiety, increased excitability or apathy and thoughts of suicide. Sibutramine has a direct effect on the brain and the central nervous system. This is how it fights overeating and excess weight. But it is not always possible to influence the psyche and nervous system without undesirable consequences. The first prescriptions for Sibutramine were accompanied by severe neuropsychiatric disorders, suicides, deaths from acute cardiac and cerebral pathologies, patients became dependent on the drug and its long-term use resulted in tragic consequences. Modern dosages of Sibutramine are much lower than those recommended at the beginning, the drug is better purified, but the undesirable effects, albeit less pronounced, still remain. During therapy with this medicine, it is forbidden to work at height, drive vehicles, or operate mechanisms that require increased concentration. This medicine is contraindicated for people with a history of alcohol or toxic addiction, since the effects will be layered.

The instructions for the drug indicate that side effects most often occurred in the first month of treatment, and if it continued, then over time the frequency and intensity of these effects decreased. Negative effects were mainly reversible and passed with the withdrawal of the drug.

The most common were: increased heart rate, hypertension, hyperemia of the skin with a feeling of warmth, constipation, complete loss of appetite, exacerbation of hemorrhoids, nausea, a feeling of dry mouth, insomnia, fainting, numbness of body parts, panic attacks, increased sweating, taste perversion.

In the post-registration study SCOUT, initiated by the relevant body of the European Union after many cases of severe side effects, in which many patients with obesity and a high probability of cardiovascular diseases took part, the following data were obtained: the risk of non-fatal (!) heart attack, stroke, heart attack in patients taking Sibutramine increases by 16% compared to those patients who took a placebo. However, what is very comforting is that with the help of resuscitation measures it was possible to save 1.4% more patients who took the real drug. But fatal cases, both from vascular pathologies and from all causes, occurred with the same frequency in both groups of patients.

There were undesirable consequences in the form of allergies from minor rashes to anaphylactic shock. The number of platelets in the blood decreased, that is, the blood did not clot well, there were cases of autoimmune damage to the walls of blood vessels (hemorrhagic purpura), mental disorders, which were already mentioned above. In these cases, it was recommended to stop the treatment.

The nervous system reacted to the drug with convulsions, short-term memory lapses, and amnesia.

Pain syndromes in the head, back, ears, visual and hearing disorders, digestion, ENT diseases, herpes. The list of side effects is endless. It ends with a message that sometimes the withdrawal syndrome is accompanied by headaches and increased appetite (!).

Women planning to have children after a course of Sibutramine should seriously think about it. The drug is teratogenic, its ability to cause mutations has not yet been confirmed, but this drug has not been used for very long and, most importantly, often unofficially. Therefore, additions to the list are still possible.

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Overdose

Taking Sibutramine doses higher than recommended increases the likelihood of adverse effects and their severity. The effects of overdose have not yet been sufficiently studied and there is no specific antidote.

As part of first aid in case of overdose, gastric lavage and enterosorbents are prescribed for an hour from the moment of taking a dose exceeding the recommended one.

It is necessary to observe the patient's condition for 24 hours after taking an excessive amount of the drug. If symptoms of side effects develop, appropriate treatment is administered. The most common consequences of an overdose, increased blood pressure and increased heart rate, are relieved with ß-blockers.
The use of an "artificial kidney" device in case of an overdose of sibutramine is inappropriate, since, as studies show, sibutramine metabolic products are practically not eliminated by hemodialysis.

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Interactions with other drugs

Not used in combination with:

• with other drugs that relieve mental pathologies or are intended for patients with alimentary obesity, which have a central effect;
• with drugs that inhibit the enzymatic activity of monoamine oxidase (there should be a time interval of at least two weeks between taking medications containing sibutramine and monoamine oxidase inhibitors);
• with drugs that stimulate the production of serotonin and suppress its reuptake;
• with drugs that inactivate liver microsomal enzymes;
• with drugs that can cause increased heart rate and increase blood pressure, as well as stimulate the sympathetic nervous system.

Preparations containing Sibutramine do not affect the pharmacodynamics of oral contraceptives.

It should also be taken into account that sibutramine and alcohol are not compatible.

Currently, in Ukraine, medicines containing Sibutramine are temporarily prohibited and their sale from pharmacies operating within the legal framework is impossible even with a prescription. However, it is not difficult to purchase drugs with Sibutramine, the Internet is full of offers. However, the sale of prohibited drugs, as well as their purchase, is punishable. This is also worth considering.

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Storage conditions

The storage conditions for Sibutramine-based drugs are no different from those for most medications. The storage temperature should not exceed 25°C, the shelf life is up to three years. The drug should not be removed from the original packaging and left in places accessible to small children.

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Analogues

The most studied drug used to treat alimentary obesity is Xenical (synonym - Orlistat). This is also an expensive analogue of Sibutramine. The active substance inhibits the absorption of fats in the small intestine, where they should be absorbed, and removes them with feces. It works only if a low-calorie diet is followed, increasing its effect by about 20%. The main side effects are expressed in intestinal upset, flatulence, fecal incontinence and directly depend on the fat content of the food consumed. The higher its fat content, the more pronounced the undesirable effects.

The difference between orlistat and sibutramine is in the mechanism of action, if the first drug mixes well with fats, removes them from the body and forces the body to use fat reserves to compensate for energy costs, then the second one reduces appetite, acting on its centers in the human brain. Sibutramine has a direct effect through the central nervous system on other body systems. Orlistat almost does not enter the general bloodstream, acting in the intestines, and has virtually no effect on the body systems. This drug is an analogue of Sibutramine only in terms of pharmacological effect - weight loss, their mechanisms of action are completely different.

The anorectic Fenfluramine is a serotonergic drug, an amphetamine derivative, closer to Sibutramine in its mechanism of action, and, accordingly, is a prohibited narcotic drug.

The antidepressant Fluoxetine inhibits the reuptake of serotonin, and therefore has anorectic properties. The list can be continued, but all of these drugs, by influencing the central nervous system, have side effects similar to Sibutramine to a greater or lesser extent, and can cause irreparable harm to health.

There are no real analogues of Sibutramine, there are cheaper synonyms of Indian production, for example, Gold Line, Redjus, Slimia. Chinese dietary supplements are definitely a "pig in a poke".

Reduksin Light has nothing in common with Sibutramine, contains the active substance oxytriptan, which has sedative and appetite-reducing properties. It is a dietary supplement.

Cheap analogues - dietary supplements Gold Line Light, Listata, which do not contain Sibutramine, but the packaging resembles sibutramine-containing products. This is more of an advertising gimmick, and accordingly, the effectiveness of these products is quite low.

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Reviews from those losing weight and doctors

Reviews of those losing weight and their relatives about Sibutramine are often frightening, side effects prompt many to stop treatment, but not everyone manages to get rid of the undesirable consequences of taking it. Judging by the reviews, these effects are not always reversible. Quite a few reviews say that people regret their decision to resort to this drug. Although there are many reviews that are clearly positive, emphasizing the high effectiveness of this substance, and, except for dry mouth, do not name any other side effects.

Doctors' reviews are quite reserved, they do not deny the high efficiency of Sibutramine, they emphasize the need to follow the rules of prescription and medical supervision of patients, self-medication is completely excluded, since the drug causes serious side effects - no one denies this. It is emphasized that half of the patients experience at least one of the side effects caused by Sibutramine. Still, it is not for nothing that this substance was banned, albeit temporarily, in most economically developed countries.