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ūüĎć Analogs of Cleocin: Cleocin Gel.

Other names for this medication:

Acnestop, Agis, Aknet, Aknezel k,  Albiotin, Anerocid,  Aniclindan,  Antirobe, Arfarel, Bactemicina, Basocin, Benzolac cl,  Bexon,  Bioclindax,  Biodaclin, Biodasin, Borophen, Botamycin-n, Candid-cl, Clamine-t,  Clendix, Cleorobe, Clidacin, Clidacin-t,  Clidamacin, Clidan, Clidets,  Climadan, Climadan acne, Clin, Clin-sanorania,  Clinacin, Clinacnyl,  Clinamicina, Clinaram, Clinbercin, Clinda, Clinda mip, Clinda-derm,  Clinda-ipp, Clinda-saar, Clinda-t,  Clindabeta, Clindabuc, Clindacin,  Clindacne, Clindacutin, Clindacyl, Clindacyn, Clindagel, Clindahexal,  Clindal,  Clindalind, Clindamax, Clindamek, Clindamicin,  Clindamicina,  Clindamycine, Clindamycinum, Clindamyl, Clindana, Clindanil,  Clindareach,  Clindasol, Clindasome, Clindastad, Clindaval,  Clindess,  Clindesse,  Clindets, Clindexcin, Clindobion, Clindopax, Clindoral,  Clindox,  Clinex, Clinfol, Clinidac, Clinika, Clinimycin, Clinium, Clinmas, Clinsol,  Clintabs, Clintopic, Clinwas, Cliofar, Cliz, Cluvax, Comdasin, Cutaclin,  Dacin, Daclin, Dalacin, Dalacine, Dalagis t,  Dalcap, Damiciclin, Damicine,  Damiclin, Dentomycin, Derma, Dermabel, Divanon, Edason, Eficline, Ethidan, Euroclin, Evoclin, Fouch, Handaramin, Indanox, Jutaclin, Klamoxyl,  Klimicin, Klin-amsa, Klindacin, Klindagol, Klindamicin,  Klindamycin,  Klindan, Klindaver, Klinoksin, Klitopsin, Lanacine, Lexis, Lindacil,  Lindacyn, Lindan, Lindasol, Lintacin s,  Lisiken, Luoqing,  Medacin,  Mediklin, Meneklin, Midocin, Milorin, Myclin, Naxoclinda, Niladacin,  Nufaclind, Opiclam, Panancocin s,  Paradis, Permycin, Prolic, Ribomin,  Rosil, Sobelin, Sotomycin, Tidact, Toliken, Topicil, Torgyn, Trexen,  Turimycin, Upderm, Veldom, Velkaderm, Ygielle, Z-clindacin,  Ziana, Zindaclin, Zindacline, Zumatic.

Indications for use
Bacterial infections caused by susceptible microorganisms: infections of upper respiratory tract infections (including tonsillitis, pharyngitis, sinusitis, otitis media); respiratory tract infections (bronchitis, pneumonia, lung abscess, pleural empyema, fibrosing alveolitis); infections of bones and joints (osteomyelitis, septic arthritis); purulent infections of the skin and soft tissues (including acne, boils, cellulitis, impetigo, felon, infected wounds, abscesses, erysipelas); sepsis (primarily anaerobic); infections of the pelvic organs and intra-abdominal infections (including peritonitis, abscesses of the abdominal organs, subject to the simultaneous use of drugs active against gram-negative aerobic microbes); gynecological diseases (endometritis, adnexitis, colpitis, abscess of the fallopian tubes and ovaries, salpingitis, pelvioperitonitis); infections of the oral cavity (including periodontal abscess); toxoplasma encephalitis, malaria (caused by Plasmodium falciparum), pneumonia (caused by Pneumocystis carinii), sepsis; endocarditis, chlamydia; scarlet fever; diphtheria.

Hypersensitivity, child age (up to 1 month) .C caution. Myasthenia gravis, bronchial asthma, ulcerative colitis (in history), severe renal and / or liver failure, pregnancy, lactation.

Pharmachologic effect
An antibiotic group of lincosamides. It has a broad spectrum of activity, bacteriostatic, binds to the 50S subunit of the ribosomal membrane and inhibits protein synthesis in the microbial cell. In respect of a number of gram-positive cocci possible bactericidal action. Active against Staphylococcus spp. (including Staphylococcus epidermidis producing penicillinase), Streptococcus spp. (excluding Enterococcus spp.), Streptococcus pneumoniae, Corynebacterium diphtheriae, spore-and non-spore-forming anaerobes, and microaerophilic gram-positive cocci (including Peptococcus spp. and Peptostreptococcus spp.), Clostridium perfringens, octrathrystheros, optus, optus, and optics, and Peptostreptococcus spp. (including Bacteroides fragilis and Prevotella melaninogenica), Fusobacterium spp., Propionibacterium spp., Eubacter spp., Actinomyces spp.

Most of the strains of Clostridium perfringens are sensitive to the drug, however, since other types of clostridia (Clostridium sporogenes, Clostridium tertium) are resistant to the action of the drug, the definition of an antibioticogram is recommended for infections caused by Clostridium spp.

It is clinically ineffective against Mycoplasma pneumoniae, Haemophilus influenzae, Helibacter pylori, Neisseria meningitidis, Neisseria gonorrhoeae, Ureaplasma urealyticum.

There is cross-resistance between the drug and lincomycin. Effective in the treatment of asymptomatic diphtheria carrier (weekly course of treatment, oral).

Side effects
On the part of the nervous system: rarely – a violation of neuromuscular conduction.

On the part of the digestive system: abdominal pain, nausea, diarrhea, vomiting, esophagitis, pseudomembranous enterocolitis, hepatotoxicity, hyperbilirubinemia, jaundice, dysbacteriosis.

From the side of blood-forming organs: leukopenia, neutropenia, agranulocytosis, thrombocytopenia.

From the side of the cardiovascular system: with a quick i.v. administration – a decrease in blood pressure, up to collapse.

Allergic reactions: rarely – maculopapular rash, urticaria, itching; in some cases, exfoliative and vesicular-dermatitis, eosinophilia, anaphylactoid reactions.

Local reactions: pain (at the site of the / m injection), thrombophlebitis (at the place of / in the injection).

Other: development of superinfection.

Special instructions
Pseudomembranous colitis can appear both on the background of the drug intake, and 2-3 weeks after stopping the treatment (3-15% of cases); manifested by diarrhea, leukocytosis, fever, pain in the abdomen (sometimes accompanied by the release of blood and mucus from the stool). If these phenomena occur in mild cases, it is enough to cancel the treatment and use of ion exchange resins (Kolestiramine, Kolestipol), in severe cases, it is shown to compensate for the loss of fluid, electrolytes and protein, the appointment of vancomycin 125-500 mg 4 times / day, or bacitracin 25 Thousands of units 4 times a day for 7-10 days, or metronidazole 500 mg 3 times a day. You can not use drugs that inhibit intestinal peristalsis.

The safety of the drug in newborns has not been established. The solution contains benzyl alcohol, which can lead to the development of asphyxiation syndrome in premature babies. According to “vital” indications, newborns are prescribed in a dose of 15-20 mg / kg / day in 3-4 doses, in some cases a smaller dose may be effective.

With long-term treatment of children requires periodic monitoring of blood counts and the functional state of the liver.

When prescribing the drug in high doses, it is necessary to control the concentration of the drug in the plasma.

It should not be prescribed for the treatment of meningitis.

Rapid i.v. administration can lead to the development of acute LV failure and a decrease in blood pressure.

Incompatible with solutions containing a complex of vitamins of group B, aminoglycosides, ampicillin, phenytoin, barbiturates, aminophylline, calcium gluconate and magnesium sulfate.

Taking the drug shows antagonism with erythromycin and chloramphenicol.

Strengthens the action of competitive muscle relaxants.

With simultaneous use with opioid (narcotic) analgesics, it is possible to increase the respiratory depression they cause (up to apnea).

The simultaneous appointment with antidiarrheal drugs that reduce gastrointestinal motility, increases the risk of pseudomembranous colitis.

Aminoglycosides expand the spectrum of antimicrobial action; enhances (mutually) the effect of rifampicin.

Cleocin Gel prescribed for the treatment of juvenile acne and other conditions. Cleocin Gel is used for treating severe acne.

Below is a list of possible side effects that can be caused by the elements that make up Cleocin Gel. This list is not final. These side effects have been reported previously, but not always fixed when using the drug. Some of these side effects can be extremely rare, but have incredibly serious consequences. If you experience any side effects, contact your healthcare professional immediately. Especially in the case of observing side effects for a long time.
– Burning
– Itchy
– Dryness
– Redness
– Oily skin
– Skin peeling
If you encounter side effects that are not listed above, contact your doctor for advice. In addition, you can report side effects to the local Food and Drug Administration.

Precautionary measures
Before you start taking this drug, tell your doctor about medicines already used, nutritional supplements (for example, vitamins, natural supplements, etc.), allergic reactions, existing diseases, and current health status (for example, pregnancy, impending surgery, etc.). Side effects of the drug may be more pronounced in a certain state of your body. Take the drug as directed by your doctor or follow the instructions for use that came with the drug. The dosage of the drug depends on your condition. Notify your doctor about the absence of changes or worsening of your condition. Important points to discuss with your doctor are listed below.
Pregnant women planning to become pregnant or breastfeeding
Children under the age of 12.

If you take other drugs or supplements at the same time as this drug, the effectiveness of Cleocin Gel may change. Tell your health care provider about all the drugs, vitamins, and nutritional supplements that you use. Your doctor will be able to make a correct plan for taking the drug, which will avoid negative interactions.

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‚ôÄActive Ingredient: Cabergoline.

‚ôÄAnalogs of Dostinex:Cabgolin.

‚ôÄOther names for this medication:
Actualene, Agalates, Cabaser, Cabaseril, Cabergolek, Cabergolin, Cabergolina, Cabergolinum, Caberlin, Caberpar, Cabeser, Cabest, Cieldom, Galastop, Kabergolin, Lac stop, Lactamax, Lactovet, Prolastat, Sogilen, Sostilar, Triaspar.

‚ôÄDostinex is used for treating disorders associated with high levels of the hormone prolactin, either due to tumors in the pituitary gland or to unknown causes.‚ôÄ

‚ôÄPharmachologic effect

Dopamine receptor agonist. Cabergoline is a dopaminergic ergoline derivative, characterized by a pronounced and prolonged prolactin-lowering effect. The mechanism of action is associated with direct stimulation of the dopamine D2 receptors of the lactotropic pituitary cells. In doses exceeding those to reduce the level of prolactin in the blood plasma, it has a central dopaminergic effect due to the stimulation of dopamine D2 receptors.

A decrease in the concentration of prolactin in the blood plasma is noted 3 hours after taking the drug and persists for 7-28 days in healthy volunteers and patients with hyperprolactinemia, and up to 14-21 days in women in the postpartum period. Prolactin-reducing action is dose-dependent both in terms of severity and duration of action.

Cabergoline has a strictly selective effect, does not affect the basal secretion of other pituitary and cortisol hormones.

Pharmacological effects of cabergoline, not related to the therapeutic effect, include only a decrease in blood pressure. With a single use of the drug, the maximum hypotensive effect is observed during the first 6 hours and is dose-dependent.


Ŕ≠Suction and distribution

After oral administration, cabergoline is rapidly absorbed from the gastrointestinal tract. Cmax in plasma is achieved in 0.5-4 hours. Binding to plasma proteins is 41-42%. Css is achieved after 4 weeks of therapy due to prolonged T1 / 2.

Meal does not affect the absorption and distribution of cabergoline.


The main product of cabergoline metabolism identified in the urine is 6-allyl-8ő≤-carboxy-ergoline at a concentration of up to 4-6% of the dose taken. The content in the urine of 3 additional metabolites does not exceed 3% of the dose. Metabolism products have a significantly lower effect in suppressing the secretion of prolactin compared to cabergoline.


T1 / 2, estimated by the rate of excretion by the kidneys, is 63-68 h in healthy volunteers and 79-115 h in patients with hyperprolactinemia.

10 days after taking the drug, 18% and 72% of the received dose are detected in the urine and feces, respectively, and the proportion of unchanged cabergoline in the urine is 2-3%.

‚ėěprevention of physiological postpartum lactation;

‚ėěsuppression of established postpartum lactation;

‚ėětreatment of disorders associated with hyperprolactinemia, including amenorrhea, oligomenorrhea, anovulation and galactorrhea;

‚ėěprolactin-secreting pituitary adenomas (micro- and macroprolactinomas), idiopathic hyperprolactinemia, ‚Äúempty‚ÄĚ Turkish saddle syndrome in combination with hyperprolactinemia.

‚ôÄDosing regimenūüďÖ
Is ingested, during meals.

Lactation prevention: 1 mg (2 tab.) Once on the first day after birth.

Suppression of established lactation: 0.25 mg (1/2 tab.) 2 times / day every 12 hours for 2 days (total dose is 1 mg). In order to reduce the risk of orthostatic hypotension in lactating mothers, a single dose of Dostinex should not exceed 0.25 mg.

Treatment of disorders associated with hyperprolactinemia: the recommended initial dose is 0.5 mg per week in 1 (1 tab.) Or 2 doses (1/2 tab., For example, on Monday and Thursday). Increasing the weekly dose should be carried out gradually – at 0.5 mg with an interval of 1 month to achieve the optimal therapeutic effect. The therapeutic dose is usually 1 mg per week, but can range from 0.25 mg to 2 mg per week. The maximum dose for patients with hyperprolactinemia is 4.5 mg per week.

Depending on tolerance, the weekly dose can be taken once or divided into 2 or more doses per week. The division of the weekly dose into several doses is recommended when prescribing the drug in a dose of more than 1 mg per week.

In patients with hypersensitivity to dopaminergic drugs, the likelihood of side effects can be reduced by starting Dostinex therapy at a lower dose (0.25 mg 1 time per week), followed by a gradual increase until the therapeutic dose is reached. To improve the tolerability of the drug in the event of severe side effects, a temporary dose reduction is possible, followed by a gradual increase, for example, by 0.25 mg per week every 2 weeks.

‚ôÄSide effect
In clinical studies using Dostinex to prevent physiological lactation (1 mg once) and to suppress lactation (0.25 mg every 12 hours for 2 days), approximately 14% of women had adverse reactions. When using Dostinex for 6 months at a dose of 1-2 mg per week, divided into 2 doses, for the treatment of disorders associated with hyperprolactinemia, the incidence of adverse reactions was 68%. Adverse reactions occurred mainly during the first 2 weeks of therapy and in most cases disappeared as therapy continued or several days after discontinuation of the drug Dostinex. Adverse reactions were usually transient, mild or moderate in severity and dose-dependent. At least once during the course of therapy, severe side effects were observed in 14% of patients; due to adverse reactions, treatment was discontinued in approximately 3% of patients.

The most frequent adverse reactions are presented below.

‚ėĀSince the cardiovascular system: heartbeat; rarely, orthostatic hypotension (with prolonged use, the drug has a hypotensive effect); asymptomatic decrease in blood pressure during the first 3-4 days after birth (systolic – more than 20 mm Hg, diastolic – more than 10 mm Hg).

‚ėĀNervous system disorders: dizziness / vertigo, headache, fatigue, drowsiness, depression, asthenia, paresthesias, syncope, nervousness, anxiety, insomnia, impaired concentration.

‚ėĀOn the part of the digestive system: nausea, vomiting, epigastric pain, abdominal pain, constipation, gastritis, dyspepsia, dryness of the oral mucosa, diarrhea, flatulence, toothache, sensation of irritation of the pharyngeal mucosa.

‚ėĀOther: mastodynia, nasal bleeding, flushing to the skin of the face, transient hemianopia, vascular spasms of the fingers, muscle cramps of the lower extremities (like other ergot derivatives, Dostinex may have a vasoconstrictor effect), blurred vision, flu-like symptoms, malaise, periorbital and peripheral swelling, anorexia, acne, pruritus, joint pain.

ūüĆěWith long-term therapy with the use of the drug Dostinex, deviation from the norm of standard laboratory parameters was rarely observed; in women with amenorrhea, a decrease in hemoglobin level was observed during the first few months after the recovery of menstruation.ūüĆě

‚ėĀThe following adverse reactions associated with the use of cabergoline were registered in the post-marketing study: alopecia, increased blood CPK activity, mania, dyspnea, edema, fibrosis, abnormal liver function, abnormal liver function, hypersensitivity, rash, respiratory disorders, respiratory failure, valvulopathy, pathological addiction to gambling, hypersexuality, increased libido, aggressiveness, psychotic disorders, pericarditis, bouts of sudden sleep, decrease or increase in body weight, nasal congestion.

ūüćďHypersensitivity to cabergoline or other components of the drug, as well as to any ergot alkaloids;

ūüćďdysfunction of the heart and respiration due to fibrous changes or the presence of such conditions in history;

ūüćďduring long-term therapy: anatomical signs of valvular pathology of the heart (such as thickening of the valve leaflet, narrowing of the valve lumen, mixed pathology of narrowing and stenosis of the valve), confirmed by echocardiography (EchoCG), conducted before the start of therapy;

ūüćďlactose intolerance, lactase deficiency, glucose-galactose malabsorption;

ūüćďchildren and adolescents under 16 years of age (safety and efficacy have not been established).

Dostinex should be administered with caution in the following conditions and / or diseases:

ūüćďarterial hypertension that developed during pregnancy, for example, preeclampsia or postpartum arterial hypertension (Dostinex is prescribed only in cases where the potential benefit from the use of the drug significantly exceeds the possible risk);

ūüćďsevere cardiovascular diseases, Raynaud’s syndrome;

ūüćďpeptic ulcer, gastrointestinal bleeding;

ūüćďsevere liver failure (the use of lower doses is recommended);

ūüćďsevere psychotic or cognitive impairment (including in history);

ūüćďsimultaneous use with drugs that have a hypotensive effect (due to the risk of orthostatic hypotension).

‚ôÄUse during pregnancy and lactation
Since there have been no controlled clinical trials with the use of the drug Dostinex in pregnant women, the prescription of the drug during pregnancy is possible only in cases of emergency, when the expected benefit to the mother outweighs the potential risk to the fetus.

If pregnancy has occurred on the background of treatment with Dostinex, the feasibility of discontinuing the drug should be considered, also taking into account the benefit / risk ratio.

According to available data, the use of Dostinex in a dose of 0.5-2 mg per week for disorders associated with hyperprolactinemia was not accompanied by an increase in the frequency of miscarriages, premature birth, multiple pregnancy and congenital malformations.

There is no information about the release of the drug in breast milk, however, in the absence of the effect of using the drug Dostinex to prevent or suppress lactation, breastfeeding should be abandoned. For disorders associated with hyperprolactinemia, Dostinex should not be prescribed to mothers who do not want to stop lactation.

‚ôÄApplication for violations of the liver
With caution, use the drug in severe liver failure (lower doses are recommended).

‚ôÄUse in children
Contraindications: children and adolescents under 16 years of age (safety and efficacy have not been established).

‚ôÄSpecial instructions
Before prescribing Dostinex for the purpose of treating disorders associated with hyperprolactinemia, it is necessary to conduct a full study of the function of the pituitary gland.

In addition, the state of the cardiovascular system, including echocardiography, should be assessed in order to detect valvular dysfunction asymptomatic.

As with the use of other ergot derivatives, pleural effusion / pleural fibrosis and valvulopathy were observed in patients after long-term administration of cabergoline. In some cases, patients received prior therapy with dopamine ergotonin agonists. Therefore, Dostinex should not be used in patients with existing signs and / or clinical symptoms of dysfunction of the heart or respiration associated with fibrotic changes or with such a history. The drug should be discontinued if there are signs of the appearance or worsening of blood regurgitation, narrowing of the lumen of the valves or thickening of the valve leaflets.

It was found that ESR increases with the development of pleural effusion or fibrosis. If an unexplained increase in ESR is detected, a chest X-ray is recommended. A study of the concentration of creatinine in the blood plasma and an assessment of renal function can also help in the diagnosis. After discontinuation of Dostinex in patients with pleural effusion / pleural fibrosis or valvulopathy, symptoms improved.

It is not known whether cabergoline can worsen the condition of patients with signs of blood regurgitation. Cabergoline should not be used in the detection of fibrous lesions of the valvular apparatus of the heart.

Fibrotic disorders can develop asymptomatically. In this regard, the condition of patients receiving long-term treatment with cabergoline should be regularly monitored and special attention should be paid to the following symptoms:

‚ėěpleural-pulmonary disorders: such as shortness of breath, difficulty breathing, persistent cough or chest pain;

‚ėěrenal failure or obstruction of the vessels of the ureters or abdominal organs, which may be accompanied by pain in the side or lumbar region and edema of the lower extremities, any swelling or tenderness in the abdominal region, which may indicate the development of retroperitoneal fibrosis;

‚ėěpericardial fibrosis and fibrosis of the valves of the heart often manifest heart failure. In this regard, it is necessary to exclude fibrosis of the valves of the heart (and constrictive pericarditis) at the onset of symptoms of heart failure.

It should regularly monitor the patient’s condition for the development of fibrotic disorders. The first time EchoCG should be performed 3-6 months after the start of therapy. Then this study should be conducted depending on the clinical assessment of the patient’s condition, paying particular attention to the symptoms described above, at least every 6-12 months of therapy.

The need for other monitoring methods (for example, physical examination, including auscultation of the heart, radiography, computed tomography) is assessed individually for each patient.

With increasing doses, patients should be under the supervision of a physician in order to establish the minimum effective dose that provides a therapeutic effect.

After an effective dosing regimen is selected, it is recommended to regularly (once a month) determine the serum prolactin concentration. Normalization of prolactin concentration is usually observed within 2-4 weeks of treatment.

After discontinuation of Dostinex, there is usually a relapse of hyperprolactinemia, however, in some patients persistent inhibition of prolactin concentration is observed for several months. In most women, ovulatory cycles persist for at least 6 months after discontinuation of Dostinex.

Dostinex restores ovulation and fertility in women with hyperprolactinemic hypogonadism. Since pregnancy can occur before menstruation is restored, it is recommended that pregnancy tests be performed at least once every 4 weeks during the amenorrhea period, and after menstruation is restored – every time there is a delay in menstruation for more than 3 days. Women who want to avoid pregnancy should use barrier methods of contraception during treatment with Dostinex, as well as after discontinuation of the drug before repeating anovulation. Women who have become pregnant should be supervised by a physician in order to identify the symptoms of an increase in the pituitary gland in a timely manner, since an increase in the size of existing pituitary tumors is possible during pregnancy.

Dostinex should be administered in lower doses to patients with severe hepatic insufficiency (Child-Pugh class C), who have been given prolonged therapy with the drug. With a single dose of 1 mg in these patients, an increase in AUC was observed compared with healthy volunteers and patients with less severe hepatic insufficiency.

The use of cabergoline causes drowsiness. In patients with Parkinson’s disease, the use of dopamine receptor agonists can cause sudden sleep. In such cases, it is recommended to reduce the dose of the drug Dostinex or discontinue therapy.

Studies on the use of the drug in elderly patients with disorders associated with hyperprolactinemia, was not conducted.

‚ôÄUse in Pediatrics

The safety and efficacy of the drug in children and adolescents under 16 years of age has not been established.

Influence on ability to drive motor transport and control mechanisms

Patients taking the drug Dostinex should refrain from driving vehicles and mechanisms and other potentially dangerous activities requiring concentration of attention and speed of psychomotor reactions.


Symptoms (more likely, symptoms of dopamine receptor hyperstimulation): nausea, vomiting, dyspeptic symptoms, orthostatic hypotension, confusion, psychosis, hallucinations.

Treatment: should carry out activities aimed at removing the drug (gastric lavage) and to maintain blood pressure. The use of dopamine antagonists is recommended.

‚ôÄDrug interaction

Information about the interaction of cabergoline and other ergot alkaloids is absent, therefore the simultaneous use of these drugs during long-term therapy with Dostinex is not recommended.

Since cabergoline has a therapeutic effect by direct stimulation of dopamine receptors, the drug cannot be administered simultaneously with drugs acting as dopamine antagonists (including phenothiazines, butyrophenones, thioxanthenes, metoclopramide), because they can weaken the effect of cabergoline, aimed at reducing the concentration of prolactin.

Like other ergot derivatives, cabergoline cannot be used simultaneously with macrolide antibiotics (for example, with erythromycin), since this can lead to an increase in the system bioavailability of cabergoline.

‚ôÄTerms and conditions of storage
The drug should be stored out of reach of children at a temperature not exceeding 25 ¬į C. Shelf life – 2 years.

‚ôÄPharmacy sales terms
The drug is available without a prescription.

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‚Ä£ Active Ingredient: Anastrozole.

‚áĚ Arimidex is used for treating breast cancer in women who have been through menopause, including women with disease progression after tamoxifen therapy. ‚áú

‚Ä£ Other names for this medication:
Anastrol, Anastrozolo, Anastrozolum, Armidex.

‚Ä£ Clinico-pharmacological group
Antitumor drug. Aromatase Inhibitor.

‚Ä£ Pharmachologic effect
Highly selective nonsteroidal aromatase inhibitor. Aromatase is an enzyme with which in postmenopausal women, androstenedione in peripheral tissues is converted into estrone and then into estradiol. Reducing circulating estradiol has a therapeutic effect in patients with breast cancer. In postmenopausal medication in a daily dose of 1 mg causes a decrease in estradiol levels by 80%.

Arimidex does not possess progestogenic, androgenic and estrogenic activity.

Arimidex in a daily dose of up to 10 mg has no effect on the secretion of cortisol and aldosterone (therefore, the use of the drug does not require the replacement of corticosteroids).

‚Ä£ Pharmacokinetics

After oral administration, anastrozole is rapidly absorbed from the gastrointestinal tract. Cmax in plasma is reached within 2 hours (on an empty stomach). Food somewhat reduces the rate, but not the degree of absorption. Small changes in the rate of absorption do not lead to a clinically significant effect on the Css of the drug in plasma with a daily intake of 1 tab. Arimidex.

Anastrozole is associated with plasma proteins by 40%. Approximately 90-95% of –°ss is achieved after 7 days of taking the drug. There is no information about the cumulation of the drug and the dependence of the pharmacokinetic parameters of anastrozole on time and dose.

Anastrozole is metabolized by N-dealkylation, hydroxylation and glucuronization. Triazole, the major metabolite detected in plasma, does not inhibit aromatase.

Anastrozole is displayed slowly, T1 / 2 – 40-50 h.

Anastrozole and its metabolites are excreted mainly with urine (less than 10% of the excreted dose – unchanged), within 72 hours after taking the drug.

‚ėěPharmacokinetics in special clinical situations

The determined clearance of anastrozole after oral administration in volunteers with stabilized liver cirrhosis or renal dysfunction does not differ from clearance determined in healthy volunteers.

Anastrozole pharmacokinetics does not depend on age in postmenopausal women.

‚Ä£ Indications
‚ėěadjuvant therapy for early hormone-positive breast cancer in postmenopausal women;

‚ėětreatment of advanced breast cancer in postmenopausal women;

‚ėěadjuvant therapy for early hormone-positive breast cancer in postmenopausal women after tamoxifen therapy for 2‚Äď3 years.

‚Ä£ Contraindications

‚ėěrenal failure severe (creatinine clearance less than 20 ml / min);

‚ėěmoderate and severe liver failure (safety and efficacy not established);

‚ėěconcomitant therapy with tamoxifen;

‚ėěchildren’s age (safety and efficacy not established);


‚ėělactation (breastfeeding);

‚ėěHypersensitivity to anastrozole and other components of the drug.

The drug is not prescribed to women in premenopausal women.

‚Ä£ Dosage
Adults, including elderly patients, the drug is prescribed 1 mg orally 1 time / day, long-term. If there is evidence of disease progression, the drug should be discontinued. As adjuvant therapy, the recommended duration of treatment is 5 years.

Patients with mild and moderately severe renal impairment do not require dose adjustment.

Patients with mild hepatic impairment do not require dose adjustment.

The tablet should be swallowed whole and washed down with water. It is recommended to take the drug at the same time of day.

‚Ä£ Side effects
ūüĎ£ Determination of the frequency of adverse reactions: very often (> 10%); often (1-10%); rarely (0.1-1%); very rarely (<0.1%).

ūüĎ£ Since the cardiovascular system: very often – tides.

ūüĎ£ From the musculoskeletal system: often – arthralgia.

ūüĎ£ Reproductive system: often – vaginal dryness; rarely, vaginal bleeding (mainly during the first weeks after the cancellation or change of previous hormonal therapy with Arimidex).

ūüĎ£ On the part of the digestive system: often – nausea, diarrhea; rarely – anorexia, vomiting, increased activity of GGT and alkaline phosphatase.

ūüĎ£ On the part of the nervous system: often – headache, carpal tunnel syndrome (mainly observed in patients with risk factors for this disease); rarely – drowsiness.

ūüĎ£ Metabolism: rarely – hypercholesterolemia. The drug may cause a decrease in bone mineral density due to a decrease in circulating estradiol, thereby increasing the risk of osteoporosis and bone fractures.

ūüĎ£ Dermatological reactions: often – thinning hair, skin rash; very rarely – erythema multiforme (Stevens-Johnson syndrome).

ūüĎ£ Allergic reactions: very rarely – angioedema, urticaria, anaphylactic shock.

ūüĎ£ Other: often – asthenia.

‚Ä£ Overdose
Single clinical cases of drug overdose are described. A single dose of Arimidex, at which life-threatening symptoms develop, has not been established.

Treatment: there is no specific antidote. If necessary, carry out symptomatic therapy: induction of vomiting (if the patient is conscious), general supportive therapy, monitoring the patient and monitoring the function of vital organs and systems. Dialysis is possible.

‚Ä£ Drug interaction
Clinical studies on drug interactions with antipyrine and cimetidine indicate that co-administration of Arimidex with other drugs is unlikely to lead to a clinically significant interaction due to cytochrome P450.

There is no clinically significant drug interaction when taking Arimidex at the same time as other frequently prescribed drugs.

At the moment there is no information on the use of Arimidex in combination with other anticancer drugs.

Estrogen containing preparations should not be administered concurrently with Arimidex, since they reduce the pharmacological effect of the latter.

Tamoxifen should not be given at the same time as Arimidex, since it may weaken the pharmacological action of the latter.

‚Ä£ Special instructions
In women with a receptor-negative estrogen tumor, the efficacy of Arimidex has not been demonstrated, unless there was a prior positive clinical response to tamoxifen.

In case of doubts about the hormonal status of the patient, the menopause must be confirmed by determining the sex hormones in the blood serum.

There are no data on the safety of Arimidex in patients with severe liver dysfunction or in patients with severe renal insufficiency (CC less than 20 ml / min).

In case of persistent uterine bleeding while receiving Arimidex, consultation and supervision of a gynecologist is necessary.

Drugs containing estrogen should not be administered simultaneously with Arimidex.

By lowering the level of circulating estradiol, Arimidex can cause a decrease in bone mineral density.

In patients with osteoporosis or with the risk of osteoporosis, bone mineral density should be assessed by means of densimetry (for example, DEXA scan) at the beginning of treatment and over time. If necessary, treatment or prevention of osteoporosis should be initiated under the close supervision of a physician.

There is no data on the simultaneous use of anastrozole and preparations of GnRH analogues.

It is not known whether anastrozole improves the results of treatment when used in combination with chemotherapy.

Safety data for long-term treatment with anastrozole has not yet been obtained.

With the use of Arimidex, ischemic diseases were observed more frequently than with tamoxifen therapy, but no statistical significance was noted.

The efficacy and safety of Arimidex and tamoxifen, when applied simultaneously, regardless of the status of hormone receptors, are comparable to those of tamoxifen alone. The exact mechanism of this phenomenon is not yet known.

Use in Pediatrics

Safety and efficacy of the drug in children have not been established.

Influence on ability to drive motor transport and control mechanisms

Some side effects of Arimidex, such as asthenia and drowsiness, may adversely affect the ability to perform work that requires increased concentration of attention and quickness of psychomotor reactions. In this regard, it is recommended that when these symptoms appear, caution should be exercised when driving a car or moving machinery.

‚Ä£ Pregnancy and lactation
The drug is contraindicated for use during pregnancy and lactation (breastfeeding).

‚Ä£ Use in childhood
The drug is contraindicated for use in children (safety and efficacy not established).

‚Ä£ In case of impaired renal function
Patients with mild and moderately severe renal impairment do not require dose adjustment.

Contraindicated in severe renal failure (creatinine clearance less than 20 ml / min).

‚Ä£ With abnormal liver function
Patients with mild hepatic impairment do not require dose adjustment.

Contraindicated in moderate or severe liver failure (safety and efficacy not established).

‚Ä£ Pharmacy sales terms
The drug is available without a prescription.

‚Ä£ Terms and conditions of storage
The drug should be stored out of reach of children at a temperature not exceeding 30 ¬į C. Shelf life – 5 years.

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Active Ingredient: Disulfiram.

Other names for this medication:

Alcophobin, Anticol, Aversan, Diabuse, Disulfiramo, Disulfiramum, Disulphiram, Esperal, Etabus, Etiltox, Refusal, Tenutex.

In 1 tablet of disulfiram 200 mg (400 mg).

Corn starch, povidone, sodium bicarbonate, talc, silicon dioxide, tartaric acid, magnesium stearate, MCC, – as auxiliary substances.

Pharmachologic effect

Pharmacodynamics and pharmacokinetics

Inhibits acetaldehyde dehydrogenase, which is involved in the metabolism of ethyl alcohol. The delay in the oxidation of ethyl alcohol at the stage of acetaldehyde causes its accumulation and the development of intoxication – a disulfiram-alcohol reaction, which is accompanied by severe sensations and violent vegetative reactions: pulsating headache, noise in the head, tachycardia, a decrease in blood pressure, heartbeat, blurred vision, nausea, vomiting .
Discomfort associated with alcohol intake, lead to a conditioned reflex aversion of alcoholic beverages.


Absorbed 70‚Äď90% after ingestion. It is well soluble in lipids and accumulates in fat depots. It is rapidly metabolized, and as a result, during a series of transformations, it is converted into an active metabolite, methyl diethylthiocarbamic acid ester (methyl DTK). The maximum concentration of which in the blood is determined after 4 hours, however, activity towards acetaldehyde dehydrogenase is noted after 3 days of regular administration.

T1 / 2 methyl-DTC – 10 h, but the activity with respect to aldehyde dehydrogenase lasts longer. Therefore, after drug withdrawal, the effect will remain 7-14 days. Metabolites are excreted in the urine, partly with exhaled air, and 20% of unchanged disulfiram through the intestine.

Indications for use
Antabuse is used to prevent recurrence in the treatment of chronic alcoholism and alcohol dependence.


Absolute contraindications:
– neuritis of the auditory and optic nerve;

– diseases of the cardiovascular system (marked cardiosclerosis, post-infarction conditions, cerebral arteriosclerosis, aortic aneurysm, hypertension);

– polyneuritis of any origin;

– emphysema, bronchial asthma;
pulmonary tuberculosis;

– mental illness, epilepsy and epileptiform syndrome;

– severe hepatic and renal failure;

– thyrotoxicosis;

– diseases of the blood-forming organs;

– aggravation of peptic ulcer disease;

– malignant tumors;

– pregnancy;

– hypersensitivity.

Other cardiovascular diseases, over 60 years of age, peptic ulcer in remission, consequences of strokes with residual effects, history of antabuse psychoses, are relative contraindications.

Side effects

Antabuse can cause the following reactions due to the action of disulfiram:
– hepatitis;

– metallic taste in the mouth;

– polyneuritis of the lower extremities;

– memory loss, headaches;

– asthenia;

– optic neuritis;

– skin manifestations.

Reactions due to the joint intake of disulfiram and alcohol:

– respiratory failure;

– heart rhythm disorders;

– myocardial infarction, angina;

– cardiovascular collapse;

– swelling of the brain;

– thrombosis of cerebral vessels;

– psychosis.

Instructions for use Antabuse (method and dosage)
Tablets are taken orally, dissolved in 0.5 cups of water. Take 200‚Äď500 mg 1‚Äď2 times a day, prescribed by a doctor. A week later, a disulfiram-alcohol sample is taken ‚ÄĒ in parallel with taking 500 mg of Antabuse, the patient drinks 20‚Äď30 ml of vodka. Observe the reaction of the body, and with a weak reaction, the dose of alcohol is increased by 20 ml. The sample is repeated several times, while adjusting the dose of alcohol and the drug. In the future, apply a maintenance dose of 200 mg / sutot 1 year to 3 years.

Instructions for use Antabuse contains warnings that the drug is prescribed after the examination and the mandatory warning of the patient about complications. With prolonged therapy may develop psychosis, thrombosis of cerebral vessels, acute polyneuritis.

An overdose of disulfiram increases the severity of reactions and leads to depression of the nervous system (coma), the development of neurological and cardiovascular complications. Symptomatic therapy is carried out.

An unacceptable combination is the intake of alcoholic beverages, alcohol-containing drugs and products, since an intolerance reaction occurs.

Metronidazole, Tinidazole, Ordinazole, Secnidazole, while taking it with Antabuse, cause delirious disorders and disorders of consciousness.

When taken with phenytoin, a significant rise in its plasma level occurs with the development of toxic symptoms.

The anti-tuberculosis drug Isoniazid may cause poor coordination.

Antabuse increases the effect of oral anticoagulants (Warfarin), and therefore there is a risk of bleeding.

Disulfiram inhibits the metabolism of Theophylline, so its dose should be reduced.

Potentiates the sedative effect of benzodiazepines (Chlordiazepoxide and Diazepam), the dosage of which should be reduced.

Storage conditions
At a temperature not exceeding 30 ¬į C.

Shelf life
5 years.

Antabuse Reviews
Anti-recurrent and supportive treatment of alcoholism is carried out by drugs: Disulfiram, Naltrexone and Acamprosate. The innovative form of disulfiram is ‚Äúeffervescent‚ÄĚ Antabus tablets, which dissolve in water, have no taste or smell. When taken together with alcohol, the drug causes unpleasant (aversive), painful sensations: fear of death, shortness of breath, feeling of lack of air and so on. The fear of death – the main manifestation of the action of disulfiram – forces the alcoholic to stop drinking alcohol.

Reviews of doctors boil down to a warning about serious complications of disulfiram-alcohol reaction. Given this and a large number of contraindications, the drug is prescribed only by a doctor, and the treatment should be under the supervision of a narcologist. It is impossible to carry out treatment independently in secret from the patient, since the phenomena caused by the preparation can be so pronounced that reanimation measures will be required. The patient should be informed that drinking a small dose of alcohol while taking Antabuse can be fatal. Before the appointment of the drug to conduct an examination and the patient must confirm that he wants to get rid of alcoholism.

Doctors remind that, unfortunately, there are no sufficiently effective medicines that suppress the craving for ethyl alcohol. And this method is not a treatment, but a ‚Äúprohibitive method‚ÄĚ, so that the patient does not have a path to retreat, and has the opportunity to achieve stable remission. Treatment of alcoholism should be comprehensive (psychological assistance, acupuncture, sedatives and a great desire to stop drinking). And reviews about the Antabuse – proof of this. Many patients took it for several years, but the craving for alcohol persisted, and only the fear of physical pain and death restrained them.

‚ÄúI took it 5 years ago under the control of a narcologist and a psychologist. I was torn off several times, but now I can control myself – the psychologist helps ‚ÄĚ

‚ÄúThere was always a craving for alcohol, but Antabus always restrained me and stopped me.‚ÄĚ

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Analogs of Levitra.

Active Ingredient: Vardenafil.

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Levitra Professional instruction.

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Active Ingredient: Diclofenac

Analogs Of Diclofenac Gel: Voltaren.

Clinical and pharmacological group.
NSAIDs for external use

Pharmachologic effect
NSAIDs for external use.

Diclofenac has pronounced analgesic and anti-inflammatory properties. By indiscriminately inhibiting the enzymes of COX-1 and COX-2, it breaks the metabolism of arachidonic acid and the synthesis of prostaglandins, which are the main link in the development of inflammation.

Used to eliminate the pain syndrome and reduce the swelling associated with the inflammatory process. When topical application causes weakening or disappearance of pain in joints at rest and during movement. Reduces the morning stiffness and swelling of the joints, contributes to an increase in the volume of movements.

With the recommended method of applying the drug, no more than 6% of diclofenac is absorbed.

↬ Post-traumatic inflammation of soft tissues and joints due to stretching, overstrain and bruises;

↬ rheumatic diseases of soft tissues (including tendovaginitis, bursitis, lesion of periarticular tissues);

↬ Pain syndrome and puffiness associated with diseases of muscles and joints (including rheumatoid arthritis, osteoarthritis, radiculitis, lumbago, sciatica);

↬ muscular pain of rheumatic and non-rheumatic origin (for a 5% gel).

↬ violation of the integrity of the skin;

↬ indication in an anamnesis for seizures of bronchial asthma after application of NSAIDs and salicylates (including acetylsalicylic acid);

↬ III trimester of pregnancy;

↬ lactation period;

‚ܨ children’s age till 6 years;

↬ hypersensitivity to diclofenac or other components of the drug;

↬ Hypersensitivity to salicylates (including to acetylsalicylic acid) or other NSAIDs.

With caution should be used in patients with hepatic porphyria (exacerbation), erosive and ulcerative lesions of the gastrointestinal tract, severe violations of liver and kidney function, chronic heart failure, bronchial asthma, in the first and second trimesters of pregnancy, in elderly patients.

Additionally for the preparation in the form of a gel 5%: with caution should be used for violations of blood clotting (including hemophilia, lengthening bleeding time, a tendency to bleeding).

Outwardly. The amount of the drug depends on the size of the painful area. A single dose of 1% gel is 2-4 g (comparable in volume to the size of a cherry or walnut). A single dose of the gel is 5% – up to 2 g (about 4 cm with the tube open completely open).

Adults and children over the age of 12 years, the drug should be applied to the skin 3-4 times / day and lightly rub.

For children aged 6 to 12 years, the preparation in the form of a gel 1% should be applied to the skin no more than 2 g (per application) up to 2 times / day; the preparation in the form of a gel 5% – no more than 1 g (about 2 cm with a fully open neck of the tube) for one application up to 2 times / day.

After applying the product, the hands should be washed.

The duration of treatment depends on the indications and the effect observed. After 2 weeks of use, consult a physician.

Side effects
Local reactions: eczema, photosensitivity, contact dermatitis (itching, redness, swelling of the treated area of ‚Äč‚Äčthe skin, papules, vesicles, peeling).

Systemic reactions: generalized skin rash, allergic reactions (hives, angioedema, bronchospastic reactions), photosensitization.

Extremely low systemic absorption of active components of the drug with external application makes an overdose almost impossible.

Symptoms: with the accidental ingestion of large amounts of gel (more than 20 g), there may be systemic adverse reactions that are characteristic of NSAIDs.

Treatment: should wash the stomach, take activated charcoal.

Drug Interactions
The drug may enhance the effect of drugs that cause photosensitivity.

Clinically significant interaction with other drugs has not been described.

Special instructions
The gel should only be applied to intact skin, avoiding contact with open wounds.

After applying, do not apply an occlusive dressing.

Do not allow the product to get into the eyes and mucous membranes.

With prolonged use of large amounts of the drug, it is impossible to exclude the occurrence of systemic side effects, characteristic for NSAIDs.

Pregnancy and lactemia
Contraindicated use of the drug in the III trimester of pregnancy. Use in I and II trimesters is possible only after consultation with a doctor.

Experience in using the drug during lactation is not available.

Application in childhood
Contraindicated in children under 6 years.

In case of violations of kidney function
With caution should apply the drug in severe violations of kidney function.

With violations of liver function
With caution should be used in patients with hepatic porphyria, severe violations of liver function.

Conditions of leave from pharmacies
The drug is approved for use as a means of OTC.

Terms and conditions of storage
The drug should be stored in a dry place inaccessible to children at a temperature of 15 ¬į to 25 ¬į C; Do not freeze. Shelf life – 2 years.

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Other names for this medication :
Aciban-dsr, Adzole-dm, Agilam, Apentral, Apuldon, Arcelenan, Atidon,  Avizol-d, Avomit, Benzilum, Bip√©ridys, Bompy, Canozol-d, Cilroton, Cinet,  Cobaperidon, Costi, Cosy, Coszol-d, Dalic, Dany, Deflux, Degut,  Depam,  Diocid-d, Docivin, Dolium, Dombaz, Domedon, Domepraz, Domerdon,  Dometa, Dometic, Domezol, Domilin, Domilux, Domin, Dominal, Dominat, Dompan, Domped, Dompel, Dompenyl, Domper, Domperdone,  Domperidona, Domperidoni maleas, Domperidonmaleat, Domperidonum.

Motilium – antiemetic drug, which is able to stimulate the motility of the gastrointestinal tract.

The drug for children and adults alleviates the condition with nausea, heartburn, vomiting, belching, bloating, heaviness in the stomach and excessive gas generation. When poisoning and the above conditions, Motilium restores disturbed processes and accelerates recovery.

Produced in the form of tablets, coated with a shell and suspension for oral administration. Before using the drug to treat children should consult a pediatrician, there are contraindications.

The active substance Motilium quickly absorbed and reaches the maximum presence in the blood plasma within an hour after taking the medication. Reduced acidity of the stomach worsens the absorption of the drug.

Domperidone does not accumulate in the body, is completely metabolized in the digestive tract and liver and is excreted with waste of vital activity. At oral intake with urine, up to 31% of domperidone is excreted, with feces – up to 66%. A small fraction of the substance is excreted from the body in its original form. Half-life in a healthy person is about 8 hours.

The study of distribution of the drug on experimental animals indicates a low penetration of domperidone into the brain. Data on the pharmacokinetics of the drug were obtained in the study of adult volunteers.

Indications for use
What helps? Motilium is used in diseases of the upper parts of the digestive tract, which reduce motor-evacuation functions.

Indications for use:

‚ėõ abdominal pain;
‚ėõ bloating;
‚ėõ feeling of overfilling in epigastrium;
‚ėõ heartburn, flatulence;
‚ėõ frequent regurgitation, cyclic vomiting;
‚ėõ nausea and vomiting caused by a violation of diet or drug therapy;
‚ėõ disruption of the stomach in children;
‚ėõ a complex of dyspeptic symptoms that are associated with a slowdown in gastric emptying.
Suspension is used for gastrointestinal reflux and regurgitation in newborns.

Use in pregnancy and lactation
Data on the use of Motilium during pregnancy is not enough.

To date, there is no evidence of an increased risk of human developmental malformations. Nevertheless, Motilium should be prescribed during pregnancy only in cases where the expected benefit of therapy for the mother exceeds the potential risk to the fetus.

In women, the concentration of domperidone in breast milk is 10-50% of the corresponding plasma concentration and does not exceed 10 ng / ml. The total amount of domperidone excreted into breast milk is less than 7 őľg / day when the maximum permissible doses are applied. It is not known whether this level has a negative effect on newborns. Therefore, if you need to use the drug Motilium during lactation, breastfeeding should be discontinued.

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Allopurinol (Embarin).
Active Ingredient: Allopurinol.

Allopurinol is a drug that has anti-gout effect on the body and helps to reduce the concentration of uric acid.

Analog: Zyloprim.

Other names for this medication: Adenock, Aideito, Alfadiman, Allo, Allo-puren, Allobenz, Allobeta, Allohexal, Allopim, Alloprim, Allopur, Allopurin, Allopurinolo, Allopurinolum, Allozym, Allural, Allurit, Aloprim, Alopurinol, Aloral, Alositol, Aluline, Apo-allopurinol, Apurin, Apurol, Atisuril, Bleminol, Caplenal, Capurate, Cellidrin, Cosuric, Dabroson, Darzune, Embarin, Epidropal, Etindrax, Foligan, Geapur, Gichtex, Hamarin, Lopurin, Lysuron, Masaton, Mephanol, Milurit, Progout, Remid, Riball, Rimapurinol, Sigapurol, Suspendol, Urbol, Uredimin, Uribenz, Uricemil, √ľrikoliz, Uripurinol, Uriscel, Urobenyl, Urosin, Urtias, Vedatan, Xanthomax, Zylol, Zyloric

Form of the preparation
The drug Allopurinol is available in the form of coated tablets, with a dosage of 100 and 300 mg.

Pharmacological properties of the drug
Tablets Allopurinol when ingested contribute to the dissolution of urate stones and reduce the concentration of urea in the body.

When taking a single dose, the maximum concentration of the main active ingredient, allopurinol, in serum is reached after 5 hours. The active substance of the drug quickly breaks down into metabolic products, and some of it is eliminated naturally through the kidneys.

Indications for use of the drug
‚Ė∂ The main indications for the use of Allopurinol pills are the following:

‚úß An increased concentration of uric acid in the blood serum – this condition is checked by means of blood tests that are given up on an empty stomach;
‚úß Identified stones and sand in the urinary tract and kidneys – the drug is shown only if the stone does not overlap the ureter, and its size does not exceed 2 mm in diameter;
‚úß Gout;
‚úß Disorders of metabolic processes in the body, namely purines and pyrimidines;
‚úß As part of complex therapy for acute and chronic myeloid leukemia;
‚úß In the complex treatment of acute leukemia;
‚úß In the complex treatment of lymphosarcoma;
‚úß Psoriasis;
‚úß Numerous injuries and pathologies of the motor apparatus, which can lead to numerous violations of metabolic processes in the body;
‚úß Side effects that develop in the patient as a result of prolonged or uncontrolled treatment with glucocorticoids or their analogues of synthetic origin;
‚úß After the passed course of chemotherapy of cancers in order to prevent the formation of urate stones in the organs of urination.

Before using this medication, you should carefully read the instructions.

‚Ė∂ Allopurinol therapy is categorically contraindicated in the following conditions:

‚úß Individual intolerance to the components of the drug;
‚úß Age to 15 years;
‚úß Hepatic or renal insufficiency in the stage of decompensation;
‚úß The period of breastfeeding or pregnancy.

Dosing and Administration
Tablets Allopurinol should be taken orally, without chewing after eating. For each individual patient, the doctor sets the optimal and effective dose, which directly depends on his diagnosis, body weight, age and the presence of concomitant pathologies. The average daily norm of the drug for an adult is from 100 to 900 mg. The number of appointments per day is determined by the doctor, but, as a rule, the tablets should be taken 2-3 times a day at regular intervals.

In pediatric practice, this drug is not used, except for persons under 15 years who undergo treatment for cancer, and they develop severe metabolic disorders, accompanied by an increased content of uric acid in the body.

Side effects
In most cases, this drug is well tolerated by the patient, provided that they accurately observe the dosage indicated by the doctor. Sometimes the patient may develop side effects during treatment with Allopurinol, which are manifested by the following symptoms:

‚ú¶ On the part of the organs of the digestive system – abdominal pain, diarrhea, vomiting, nausea, excessive salivation, inflammation of the liver and its increase in size, the development of ulcers in the oral cavity;
‚ú¶ From the side of the cardiovascular system – slowing down the number of heart beats a minute, increasing blood pressure, feeling that the patient is now suffocating;
‚ú¶ From the side of the central nervous system – increasing weakness, severe headaches or dizziness, depression and depression, apathy to what is happening, inhibition, drowsiness, decreased visual acuity;
‚ú¶ From the side of the urinary and genital system – the development of inflammatory processes of the kidney tissue, edema, uremia, a significant increase in the number of erythrocytes in the urine, resulting in a reddish color, difficulties with the onset of conception, gynecomastia in men – breast enlargement, erectile dysfunction;
‚ú¶ From the hematopoietic system – a decrease in the number of platelets in the blood test, the development of aplastic anemia, a decrease in the number of leukocytes;
‚ú¶ Allergic reactions – the appearance of rashes on the skin, itching of the skin, increased body temperature, not caused by cold or infectious diseases, pain in the joints, redness of the skin;
‚ú¶ Development of alopecia;
The appearance of boils at different parts of the body.

Special instructions
Allopurinol tablets should be given with special caution to patients who have impaired thyroid function or other endocrine system function. In addition, the tablets of this drug with caution should be taken in patients with severe impairment of kidney and liver.

During the period of treatment with this drug, the patient must closely monitor the daily amount of fluid used, which is at least 2 liters.

During the course of therapy with allopurinol, care should be taken to manage the transport, since the influence of the active substances on the central nervous system may slightly suppress or slow down the reaction rate.

Allopurinol and alcoholic drinks are absolutely incompatible, therefore, during the period of drug use, it is strictly forbidden to drink alcohol.

Storage, dispensing and shelf life of the preparation
Tablets should be stored in a dark, cool place out of the reach of children. Shelf life of the drug is 3 years from the date of manufacture, which is indicated on the package. Allopurinol is dispensed in pharmacies without a prescription.

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Other names for this medication ‚ėü 
Hypovase, Minizide, Prazopress, Prazosinum.

One tablet can contain 0.5 or 1 mg of active substance – prazosin.

Pharmachologic effect
The drug is characterized by antihypertensive and vasodilating effect.

Pharmacodynamics and pharmacokinetics
The mechanism of action of the drug is based on the ability of prazosin to block postsynaptic őĪ1-adrenergic receptors and interfere with vasoconstrictive effects of sympathetic innervation, as well as catecholamines.

Prazosin as an őĪ-adrenergic blocking drug has both an expanding effect both on the arteries and veins, a little more on voluminous venous vessels, which leads to a decrease in the venous influx to the heart and facilitating the work of the heart muscle due to a decrease in peripheral resistance. Thus, both pre- and post-loading on the myocardium decreases: a decrease in the end-diastolic pressure along the way of peripheral veins widening and a decrease in the inflow to the right atrium, and a decrease in the pressure in the aorta are observed.

The peak of the hypotensive effect as a result of taking a single dose comes on the 1-4th hour and can last up to 10 hours. In addition, it is possible to develop both early (3-5 days) and late (by 12 months) tolerance, which requires an increase in dosage.

Absorption of prazosin is from the gastrointestinal tract, with bioavailability of 50-85%. It binds to plasma proteins by 95%, then is metabolized in the liver along the way of detachment of the methyl group, conjugation to form 4 active metabolites, having 25% pharmacological activity.

Indications for use
The use of the drug is appropriate for hypertension and congestive heart failure.

‚ėě hypersensitivity to prazosin and other inactive components;
‚ėě constrictive pericarditis (squeezing);
‚ėě hypotension;
‚ėě cardiac tamponade, heart defects, characterized by reduced pressure ‚ėě‚ėě‚ėě when filling the left ventricle;
‚ėě hyponatremia;
‚ėě pregnancy or lactation;
‚ėě children’s age (up to 12 years).

Side effects
Against the background of therapy, Prazozin can develop:

‚ėõ severe hypotension;
‚ėõ tachycardia;
‚ėõ an increase in diuresis;
‚ėõ manifestations of allergic reactions;
‚ėõ dizziness, headaches, a feeling of fatigue, nausea, dry mouth, darkness in the eyes.

Long-term treatment can lead to edema of the lower extremities.

Prazosin, instructions for use (Method and dosage)
Take the tablets orally for 0.5-1 mg several times a day (2-3 times, regardless of diet), gradually increasing the dose after 3 days.

The recommended maintenance dose may vary between 3-20 mg per day (in divided form).

The phenomenon of the first dose
The use of the drug should begin with a small dose before bedtime in the amount of 0.5-1 mg. After this, the patient is recommended bed rest, since postural hypotension may develop until fainting, collapse and other reactions associated with the phenomenon of the first dose. The greatest manifestation of these reactions, if previously treated with diuretics.

Admission of overdose of the drug can lead to a marked decrease in blood pressure (BP). In this case, it is recommended to take a horizontal position and raise your legs.

‚ėõ Prazosin and Nifedipine are incompatible;
‚ėõ the hypotonic effect of Prazosin is increased under the action of diuretics, ‚ėõ sympatholytics, ő≤-adrenoblockers, increasing the risk of a strong decrease in blood pressure;
‚ėõ with Digoxin, a significant increase in its concentration in the blood plasma;
‚ėõ Indomethacin may decrease the efficacy of Prazosin;
‚ėõ simultaneous application with clonidine leads to a change in the antihypertensive effect of the latter.

Storage conditions
Should be stored in places protected from moisture and light rays, at temperatures below +25 ¬į C, out of children’s reach.

Shelf life
The drug should not be used after 3 years from the date of release.

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Analogs of Fluoxetine.

Other names for this medication:
Actan, Adofen, Alental, Apo-fluoxetin,  Astrin,  Auscap,  Bioxetin,  Depreks,  Deproxin, Diesan, Equilibrane, Erocap, Eufor, Flotina, Floxet, Flucti-nerton, Fluctin, Fluctine, Fludac, Flufran, Fluneurin, Flunil, Fluox, Fluox-puren, Fluoxac, Fluoxeren, Fluoxeron, Fluoxetina, Fluoxetinum, Fluoxil, Fluoxin, Fluseren, Flutine, Fluxet, Fluxil, Fluxonil, Fondur, Fontex, Fysionorm, Ladose, Lovan, Margrilan, Motivone, Oxetine, Pragmaten, Prodep, Pronil, Prozac, Reneuron, Rowexetina, Seronil, Zactin.

Fluoxetine tablets contain 20 mg fluoxetine, as well as lactose monohydrate, gelatin, corn starch, calcium stearate, povidone, silicon (Si) colloidal dioxide, talc, magnesium (Mg) light carbonate, tropeoline 0, additive E171 (titanium (Ti ) dioxide), mineral oil, sugar, yellow wax.

Form of issue
Tablets covered with a film coating of yellow color in blisters for 10 pcs, 1 or 2 blisters in a package.

Pharmachologic effect
The drug has an anorexigenic effect, eliminates depression and relieves feelings of depression.

Pharmacodynamics and pharmacokinetics Fluoxetine – what is it?
The active substance of the preparation fluoxetine hydrochloride is a water-soluble crystalline powder of white (or almost white) color.

What is Fluoxetine?
Fluoxetine is a selectively inhibitory reverse neuronal seizure of serotonin (ONS) agent. The drug belongs to the pharmacotherapeutic group “Antidepressants”.

The medicine is intended for oral administration. The mechanism of its action is related to the ability to selectively (selectively) and reverse the ONZS.
Antidepressant Fluoxetine slightly affects the capture of dopamine and norepinephrine and weakly affects acetylcholine receptors and H1-type histamine receptors.
Along with antidepressant also has a stimulating effect. After taking the tablets / capsules, the patient’s fear, anxiety and mental tension decrease, the mood improves, the symptoms of dysphoria are eliminated.
Wikipedia notes that the remedy does not cause orthostatic hypotension, does not have a sedative effect, is not cardiotoxic.
To achieve a stable clinical effect with regular use of the drug takes from 3 to 4 weeks.

Pharmacokinetic parameters:
‚ě°absorption in the alimentary canal – good;
‚ě°bioavailability – 60% (with oral administration);
‚ě°–Ę–°–ľ–į—Ö – from 6 to 8 hours;
‚ě°binding to plasma proteins (including alpha (őĪ) -1-glycoprotein and albumin) – 94.5%;
‚ě°T¬Ĺ – 48-72 hours.
The liver is involved in the metabolism of the substance. As a result of its biotransformation, a number of unidentified metabolites are formed, as well as norfluoxetine, the selectivity and activity of which is equivalent to that of fluoxetine.

Pharmacologically inactive metabolic products are eliminated by the kidneys.
Due to the fact that the substance is removed from the body slowly enough, the plasma concentration necessary for maintaining the therapeutic effect persists for several weeks.

Indications for use: what are the prescribed tablets and fluoxetine?
Indications for use of fluoxetine:
‚ě°depression (in particular, accompanied by fears), including with the inefficiency of other antidepressants;
‚ě°obsessive-compulsive disorder (OCD);
‚ě°kinoreksiya (to reduce uncontrolled craving for food, the remedy is used as part of complex psychotherapy).

The drug is not prescribed when:
‚ěĘknown hypersensitivity to its active substance or any of the auxiliary ‚ěĘcomponents;
‚ěĘconvulsive conditions in the anamnesis;
‚ěĘsevere liver and / or kidney failure;
‚ěĘsuicidal tendencies;
‚ěĘvatony of the bladder;
‚ěĘprostate adenoma;
‚ěĘsimultaneous application with MAO inhibitors .
After using MAO inhibitors, Fluoxetine can be used no earlier than 14 days; MAO inhibitors after the end of treatment with fluoxetine are prescribed no earlier than 5 weeks.

Side effects of fluoxetine
General disorders that occur during the use of the drug may manifest in the form of hyperhidrosis, chills, fever or cold sensation, photosensitivity, neuroleptic syndrome, alopecia, lymphadenopathy, anorexia, erythema multiforme, which can progress to malignant exudative or develop into Lyell’s syndrome.

Some patients have symptoms of serotonin intoxication, including:  ‚ě≥changes in mental status (delirium, euphoria, anxiety, agitation, hallucinations, mutism, confusion, manic syndrome, coma);
‚ě≥neuromuscular pathologies (akathisia, coordination disorders, bilateral Babinsky symptom, hyperreflexia, myoclonus, epileptiform seizures, nystagmus (horizontal and vertical), oculogic crises, paresthesia, opisthotonus, tremor, muscular rigidity);
‚ě≥vegetative dysfunction (hyperthermia, abdominal and headaches, diarrhea, dilated pupils, lacrimation, tachypnea, tachycardia, nausea, fluctuations in blood pressure, hyperhidrosis, chills).

From the digestive system of organs are possible: diarrhea, nausea, decreased appetite, vomiting, dysphagia, dyspepsia, taste change, pain in the esophagus, dry mouth, dyskinesia, liver dysfunction. In isolated cases, idiosyncratic hepatitis can develop.
CNS reactions to the taking of tablets are manifested in the form of: ‚ě£bruxism, headache, weakness, sleep disorders (nighttime delirium, pathological dreams, insomnia), dizziness, fatigue (hypersomnia, drowsiness);                                                                                                                ‚ě£violations of attention, processes and concentration of thinking, memory; anxiety and associated psychovegetative syndrome, dysphemia, panic attacks, suicidal thoughts and / or attempts to deprive oneself of life.
Reactions from the urogenital tract:                                                                  ‚ě£dysuria, urine retention, polakii-and nocturia, protein and albuminuria, polyuria, oliguria, UTI, renal failure, cystitis, decreased libido (before its complete loss), erectile dysfunction, breast enlargement and soreness , disorders of ejaculation, anorgasmia, priapism, impotence, metro- and menorrhagia, painful menstruation.
The probability of development is not excluded:
‚ě£immunopathological and allergic reactions;
‚ě£myalgia, arthralgia, chondrodystrophy, bone pain, osteomyelitis, arthritis and a number of other side effects from the musculoskeletal system;
‚ě£postural hypotension;
‚ě£metabolic disorders (including hyponatremia, hypocalcemia, hyper- or hypokalemia, vasopressin secretion disorder, diabetes mellitus, hypercholesterolemia, hyperuricemia, edema, diabetic acidosis, dehydration, hypothyroidism);
‚ě£skin reactions (including polymorphic rash, acne, ulcerative lesions of the skin, gyrustism, psoriasis, furunculosis, exfoliative dermatitis, etc.).
Discontinuation of treatment with the drug can trigger a withdrawal syndrome, the main signs of which are: sensitivity disorders, dizziness, sleep disorders, asthenia, nausea and / or vomiting, agitation, headache, tremor.
Reviews of side effects suggest that the drug with uncontrolled admission is addictive. In some cases, the dependence is so strong that a person needs the help of a specialist to treat it.
Other adverse reactions that patients mention in the reviews are severe drowsiness, tremors, convulsions, decreased appetite, nausea. Nevertheless, there are people who had no adverse effects on the background of treatment at all.

Instructions for use of fluoxetine
Tablets are taken orally. The intake of food for assimilation of the drug is not affected.
For relief of depressive symptoms, the drug should be drunk 1 time per day, in the morning, at a dose of 20 mg. With clinical need, 3-4 weeks after the start of therapy, the frequency of receptions is increased to 2 r. / Day. (tablets are taken in the morning and in the evening).

Patients with an insufficient response to treatment at a dosage of 20 mg / day, in some cases, the daily dose is gradually increased to 60-80 mg. In this case, divide it into 3-4 receptions. The highest dose for people of elderly and senile age is 60 mg / day.
Dosage for bulimic neurosis – 60 mg / day. (tablets take 3 r./day on one), in ROC – depending on the severity of clinical symptoms – from 20 to 60 mg / day.
It should be taken into account that increasing the dose may increase the severity of side effects.
The maintenance dose is 20 mg / day.

When does the drug start to act?
Significant improvement in the condition is usually observed after about 2 weeks of systematic drug intake.

How long should I take fluoxetine?
The elimination of depressive symptoms goes away from six months.
In obsessive manic disorders (HMP), the drug is given to the patient for 10 weeks. Further recommendations depend on the results of treatment. If there is no clinical effect, the fluoxetine treatment regimen is revised.
If there is a positive dynamics, therapy is continued with the use of an individually selected minimum maintenance dose. Periodically, the patient’s need for further treatment should be reviewed.
Long-term – more than 24 weeks in patients with HMR and more than 3 months in patients with bulimia nervosa – has not been studied.

General recommendations
After the treatment with Fluoxetine is completed, the active substance circulates in the body for another 2 weeks, which should be taken into account when discontinuing treatment or prescribing other medicines.
Patients with liver / kidney failure, elderly people with concomitant diseases, as well as patients taking other medicines, are prescribed a half dose of the drug. In some cases, it is advisable to transfer the patient to an intermittent reception.
It is not recommended to abruptly stop therapy with fluoxetine. The drug is canceled, gradually reducing the dose for 1-2 weeks. This avoids the development of withdrawal syndrome.
If after the dose reduction / withdrawal the patient’s condition worsens, it is necessary to return to treatment with the previous effective therapeutic dose. Gradual reduction of the dose is resumed after the appearance of positive dynamics.
If we compare Fluoxetine and Fluoxetine Lannacher or Fluoxetine and Fluoxetine OZONE, we can conclude that the instructions for the use of Fluoxetine Lannacher and Fluoxetine OZON provide recommendations similar to those listed above.

Overdosage Fluoxetine is accompanied by: nausea / vomiting, convulsions, hypomania, anxiety, agitation, large epileptic seizures.
A high dose of the drug in combination with codeine, maprotiline, temazepam can lead to death.
The person suffering from an overdose should be washed with a stomach, give sorbitol, enterosorbent and – with convulsions – diazepam. Also, monitoring of respiratory activity and parameters characterizing the functional state of the heart is important. In the future, symptomatic and supportive therapy is performed.
Peritoneal dialysis, blood transfusion, hemodialysis, forced diuresis are ineffective.

Strengthens the effects of hypoglycemic drugs, ethanol, diazepam, alprazolam.
Twice increases the plasma concentration of tricyclic antidepressants, phenytoin, trazodone, maprotiline. When appointing fluoxetine in combination with tricyclic antidepressants, the dose of the latter should be reduced by 50%.
It can provoke an increase in the plasma concentration of Li +, which in turn increases the likelihood of developing its toxic effects. In case of simultaneous application, it is recommended to keep the concentration of Li + in the blood under control.
The use as an adjunct to electroconvulsive therapy can lead to the development of prolonged epileptic seizures.
Serotonergic effects of the drug are enhanced in combination with tryptophan. The likelihood of the development of serotonin intoxication is increased in the case of simultaneous administration with agents suppressing the enzyme MAO.
The likelihood of adverse reactions and increased oppressive effects on the central nervous system increases in combination with drugs that depress the central nervous system.
Admission with drugs that have a high degree of binding to proteins can trigger an increase in the plasma concentration of unbound (free) drugs, as well as an increase in the likelihood of unwanted effects.

Storage conditions
Tablets should be stored at a temperature below 25 ¬į C.

Shelf life
5 years.

Special instructions
In the treatment of patients with low body weight, anorexic effects should be considered when prescribing the drug.
In diabetics during treatment Fluoxetine may develop hypo-, and after discontinuation of the drug – hyperglycemia. In view of this, it is recommended to make changes in the dosage regimen of insulin and / or hypoglycemic agents for oral administration. Before the improvement of the clinical picture, patients with diabetes should be under constant medical supervision.
During treatment it is necessary to refrain from engaging in activities that require high speed of psychomotor reactions and increased attention.
The composition of the tablets includes lactose, so they should not be taken with galactosemia, lactase deficiency, the syndrome of impaired glucose / galactose absorption.
Like other antidepressants, fluoxetine can cause affective disorders (mania or hypomania).

The central organ of the metabolism of the drug is the liver, the excretion of metabolites is responsible for the kidneys. Patients with liver pathologies should be prescribed low or alternative daily doses.
With renal failure (with Clcr less than 10 ml / min.) After 2 months of treatment with a dose of 20 mg / day. the plasma concentration of fluoxetine / norflouxetine is the same as in patients with healthy kidneys.
Depression is associated with an increased risk of suicidal thoughts and attempts to kill oneself. The risk persists until complete remission.     Clinical experience of the drug shows that the risk of suicide increases, usually in the early stages of recovery.
Patients with mental illness and depressive syndrome should be under constant supervision. In placebo-controlled studies, the group receiving antidepressant patients found that the risk of suicidal behavior is highest in people under 25 years of age.
Special attention is also required by patients who have been transferred to a lower / higher dose.

The use of fluoxetine is associated with the development of akathisia, the subjective features of which are the constant need to be in motion, as well as the inability to sit or stand. These phenomena are especially pronounced in the first weeks of treatment. Patients who developed similar symptoms, the drug is prescribed in the minimum effective dose.
With a sudden discontinuation, approximately 60% of patients develop withdrawal symptoms. The likelihood of their appearance depends on the dose used, the duration of the course, and the level of dose reduction. The dose is recommended to be reduced by titration within 7-14 days.
There have been reports of subcutaneous hemorrhages, such as purpura or ecchymosis, occurring during the treatment period. Therefore, patients taking oral anticoagulants, affecting the function of platelets and increasing the likelihood of hemorrhages, as well as patients with bleeding history, Fluoxetine is prescribed taking into account possible risks.

Which is better: Prozac or Fluoxetine?
The active substance of the drug Prozac is fluoxetine. Therefore, when choosing in favor of this or that tool, the decisive factors are price and subjective sensations. The cost of fluoxetine is much lower than the cost of its analogue.

For children
Not applicable for treatment of patients younger than 18 years.
A nineteen-week clinical trial showed that in children suffering from depression, 8-18 years of age, Fluoxetine causes a decrease in body height and weight. The effect of the drug on achieving normal growth in adulthood has not been studied.
At the same time, the probability of growth retardation in the pubertal period can not be ruled out.

Fluoxetine and alcohol
Drinking alcohol during treatment with fluoxetine is contraindicated.

Fluoxetine for weight loss
Fluoxetine is often prescribed for a bulimic syndrome – a mental syndrome, which is accompanied by a lack of satiety and uncontrolled overeating.
The use of the drug can reduce appetite and relieve a constant feeling of hunger.
Thus, it can be concluded that fluoxetine can get rid of excess weight only if the reason for its collection is the appetite.
However, the drug is not intended for weight loss, its main purpose is the treatment of depression. Reducing appetite and losing weight are side effects.
The drug is quite powerful, and the body often responds to its reception with anaphylactic reactions and systemic disorders involving the pathological process of the lungs, skin, kidneys and liver.

How to take fluoxetine for weight loss?
At the initial stage, diet pills are taken in the minimum dosage – one once a day. With good tolerability, you can go to the reception of two tablets – one drink in the morning, the second – in the evening.
The maximum allowable dose is 4 tab. / Day.
The drug begins to act after 4-8 hours, removing fluoxetine from the body takes about a week.
Reviews on the forums confirm the effectiveness of the means – for 1-3 months people without much effort got rid of 5-13 kg. In this case, all patients taking Fluoxetine note that it is not worth while to drink it just for the sake of losing weight, like Fenibut or Fentropil, in the absence of evidence.

In pregnancy
The safety of the drug in pregnant women is poorly understood, the results of individual published epidemiological studies are contradictory. In some random and cohort studies, there was no increase in the likelihood of congenital developmental abnormalities.
ENTIS prospective study suggests an increase in the likelihood of developing congenital anomalies in the structure of large vessels or heart in children whose mothers took fluoxetine in the 1st trimester of pregnancy, compared with children whose mothers did not receive this medication.
It was not possible to establish a reliable relationship between the use of the drug in the early stages of pregnancy and the formation of malformations in the fetus. The specific group of CCC abnormalities was also not determined.
The use of SSRIs in the last weeks of pregnancy contributes to the development of complications in newborns, in particular, the prolongation of the duration of ventilation and probe nutrition and the duration of hospitalization.
There are mentions of the development of apnea, respiratory distress syndrome, seizures, hypoglycemia, lability of body temperature and blood pressure, tremor, hyperreflexia, vomiting, cyanosis, difficulties with adequate nutrition, constant crying, excitability, nervous irritability.
The listed pathological conditions can be a consequence of the syndrome of withdrawal of SSRIs or the manifestation of their toxic effects.

Reviews of fluoxetine
Feedback from the host fluoxetine (APO, Lannacher, Kanon) patients leave the impression of the efficacy of this remedy for depression, bulimic neuroses and OCD.
At forums also the possibility of application of a preparation for the control of appetite and correction of weight is quite often discussed.
Reviews of doctors about fluoxetine for weight loss are unequivocal: you can use a medicine to fight excess pounds only if the cause of weight gain is a mental disorder.
When excess weight is the result of depression caused by stress or overeating, the drug for 2-3 weeks can completely get rid of binge eating attacks and for the first month to remove up to 5 kg.
Reviews losing weight about Fluoxetine (Lannacher, OZONE, etc.) allow you to conclude that to reduce weight on this drug is not possible to all: someone has completely lost appetite (right up to aversion in food), someone has left it the former.
However, in most cases, the remedy has serious side effects: many people who took it noted a decrease in sexual desire and a deterioration in sexual life, a sense of inhibition, severe pain, drowsiness, increased aggression, the appearance of suicidal thoughts.
In addition, for many of the debilitated drugs, the need to stop driving and drinking alcohol, and the fact that fluoxetine is highly addictive.
Summarizing reviews, the following conclusions can be drawn: Fluoxetine is primarily a cure for depression and can only be taken if there is evidence and only under the supervision of a doctor.

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