Pharmacological action

Pharmacological action An antidepressant, an inhibitor of reuptake of serotonin and norepinephrine and weakly inhibits dopamine uptake, has no significant affinity for histamine, dopamine, choline - and adrenoreceptors. The mechanism of action of DULOXETINE is in the treatment of depression is suppressing the reuptake of serotonin and norepinephrine, as a result of increased serotonergic and noradrenergic neurotransmission in the CNS. Viagra active substance: sildenafil. Viagra Viagra - drug for the treatment of erection disorders - erectile dysfunction. Operates on natural mechanisms of occurrence erectile; helps the man to cause an erection. Used in men suffering from erectile dysfunction of different origin (vascular, nerve, erectile dysfunction). Latin name: VIAGRA / VIAGRA. Composition and product form: Viagra tablets for 1 or 4 pack. 1 tablet Viagra contains 25, 50 or 100 mg of sildenafil (as sildenafil citrate). Information for patients: What is Viagra? The drug Viagra (VIAGRA) developed by Pfizer, is the first taken by mouth tableted pharmaceutical agent which exhibits significant and reliable efficacy in the majority of patients with disorders of erection. The active substance of the drug - sildenafil citrate. The drug is available in tablets of 25 , 50 and 100 mg which contain, accordingly, on 25, 50 and 100 mg of sildenafil citrate. Viagra is simple, convenient and easily used drug. When using Viagra do You just take one tablet when you plan sexual intercourse. What is the mechanism of action of Viagra? It is to increase the amount of blood flowing into the penis that helps the man to cause natural erection. Viagra works only when a man feels a natural sexual arousal, and when sexual intercourse is completed, the penis naturally returns to the relaxed state. In other words, Viagra operates only on natural mechanisms of erection and this is its undeniable novelty and secret huge popularity. How was invented Viagra? The discovery of Viagra was the greatest "accidental" discovery in medicine. The history of Viagra began in 1992 in the UK, during pharmacological research firm Pfizer. The researchers conducted clinical trials of a new drug substance is Sildenafil, which was developed as a means to treat a number of heart ailments. Scientists had hoped that the citrate of sildenafil will increase the blood flow to the heart muscle and reduce blood pressure. However, it was observed that sildenafil citrate has no significant effect neither on the circulation in the heart muscle (myocardium), nor on blood pressure. In parallel revealed that many male patients who participated in the study refused to return the tablets of sildenafil, despite the end of testing. The reason all these patients had one - they all have dramatically improved the quality of erections. What is the clinical efficacy of Viagra? According to numerous clinical research and trials on volunteers with different types of erectile dysfunction, Viagra has a relatively high efficiency. The effectiveness of Viagra in very strong degree depends on a kind erectile dysfunctions, from accompanying diseases. For example, if in vascular erectile dysfunction, the drug is quite effective, we can say that if so-called pathological venous drainage results of application much worse. Unfortunately, does not exist, and cannot exist drug that can cure all diseases, or, as in our case, all kinds of erectile dysfunction. A panacea and is not Viagra, which is able to help in a very large number of cases, but unfortunately, not all patients. Does Viagra libido? The action of Viagra is based only on local increase of blood flow in the cavernous body of the penis, and it does not cause amplification of sexual desire. It does not increase libido and is not an "exciting" tool. Viagra simply suppresses enzyme which influences a blood flow in the penis. And for her actions if you are sexually aroused. Viagra promotes the natural response of an organism to sexual stimulation. Clinical studies show the lack of amplification of attraction in the group of patients treated with the drug Viagra when compared with a control group of patients who received a placebo of the same age without taking Viagra. There is no reason to suppose that Viagra causes aggression. Who should take Viagra? Viagra is intended to apply to men suffering from erectile dysfunction of various origins - whether lesions of blood vessels or nerves of the penis. An exception may be only a rough fibrosis of the cavernous bodies of the penis, because in this case the blood flow to the penis, most likely, will not cause the patient improved and so-called pathological venous drainage of the corpora cavernosa", which resulted in the outflow of blood from the penis is too strong, making it impossible for his erection. How to determine the sexual norm? Healthy is the one who arises and persists erection, allowing him to engage in sexual intercourse and successfully complete them. Viagra returns suffering from erectile dysfunction to normal or, at least, provides a shift in this direction. If people who consider themselves healthy, accepts Viagra and finds improvement in erectile function, in fact he may suffer some erectile dysfunction, at least temporary, and it cannot be considered healthy in the precise sense of the word. How to take a Viagra? Appoints a Viagra specialist. Take Viagra is very simple. All You have to do is take one tablet about an hour before sexual activity. After about 30-60 minutes the action starts Viagra and lasts for four hours. But the action of Viagra starts only in response to sexual stimulation. The best time to take Viagra before meals because it will act faster. If You take Viagra after eating, especially if You eat fatty foods, Your body will need more time for the absorption of the drug and it will take effect later. The action of Viagra is such that you need to take it only when You want to have intercourse. Viagra should not be taken more than once a day. You should know that the drug Viagra is not an aphrodisiac and therefore just taking the pill without sexual stimulation will not cause You erection. What experts recommended to consult about taking Viagra? It is recommended to first consult a sex therapist. It is desirable that You also visited a cardiologist or internist to rule out heart disease. Also, if you suffer from any chronic diseases, you should contact the appropriate specialist and consult with him about the advisability of taking Viagra. Don't hesitate to apply to the doctors with all their questions and doubts. How to choose the right dose of viagra? The drug is available in three standard dosages: 25, 50 and 100 mg. is Quite obvious that the larger the dose, the more effective the drug. There are several approaches to the selection of the dosage of the drug. Usually the drug in high dosages of 50 mg and then, depending on coming (or not coming) effect dosage is adjusted, or, in the case of good effect, is not changed. Another approach is to start treatment with the lowest dosage, increasing it until a good therapeutic effect. How much Viagra is safe? Clinical trials have proven the safety of Viagra. However, it is known manifestation of some drug interactions, especially with nitrates used in the treatment of heart disease. Therefore, Viagra is contraindicated in patients receiving treatment with nitrates. The danger is a possible significant drop in blood pressure - hypotension. What are the data about the side effects of Viagra? As with any other drug, in the case of treatment of Viagra can appear side effects. As a result of extensive clinical research in more than 3700 patients, they demonstrated good tolerability of the drug Viagra. Most frequently reported adverse events were headache (15.8 percent) and sudden reddening of the face and neck (10,5%), dyspepsia (5,5%), which were generally transient in nature, mildly and moderately severe and necessitated discontinuation of treatment. The frequency of discontinuation of treatment because of side effects due to all causes, was comparable for patients receiving the drug Viagra (2,5%) or placebo (2.3 percent). Cases of priapism (painful, long enduring erection) in any of the clinical trials of the drug Viagra has not been reported. Who Viagra need to be taken with caution? First of all, these are people with severe diseases of the cardiovascular system (heart failure, angina pectoris, impaired cerebral circulation). These people need constant medical supervision, because sexual intercourse is a serious physical strain for a person. If you have symptoms such as pain in the heart during physical load and/or at rest, impaired memory and mental performance, progressing over the last few months, or You have already suffered a heart attack or stroke, it is mandatory You should consult with your doctor about expediency of reception Viagra. Increased caution is also needed in patients who have previously had priapism (a pathological condition which is characterized by the occurrence of erections, which are not linked to erotic stimulation, and which can last for hours, causing severe pain in the penis). Although to date, no reported reports of occurrence of priapism in patients receiving Viagra, however, patients who have a predisposition to its occurrence also medical supervision is necessary. Careful when taking Viagra necessary for people who are going after taking control of a different sort mechanisms or the automobile since sometimes after taking Viagra in humans may occur rapidly undergoing change color perception with a predominance of blue flowers. In patients with clinical signs of liver failure may slow metabolism and excretion of DULOXETINE. After a single dose of DULOXETINE at a dose of 20 mg in 6 patients with cirrhosis and moderate impaired liver function (class b on a scale child-Pugh) duration T1/2 of DULOXETINE was about 15% higher than in healthy individuals matched for age and gender with five-fold increase in average AUC. Despite the fact that the Cmax in patients with cirrhosis was the same as in healthy people, the T1/2 approximately 3 times more. Dosage The drug is taken orally. The capsules should be swallowed whole, without chewing or crushing. You cannot add the drug in food or mix with liquids, because this may cause damage to the enteric-coated pellets. The recommended initial dose of DULOXETINE is 60 mg 1 times/day regardless of the meal. Some patients to achieve a good result it is necessary to increase the dose to 60 mg 1 times/day to a maximum dose of 120 mg/day 2 reception. Systematic evaluation of the drug in the dose above 120 mg have not been conducted. In patients with chronic renal insufficiency in terminal stage (QC<30 ml/min) the initial dose is 30 mg 1 times/day. In patients with impaired liver function should reduce the initial dose of the drug or reduce the dosing frequency in patients with cirrhosis. The drug is recommended in patients older than 18 years. Clinical experience with the drug in patients over the age of 18 are not. Avoid abrupt discontinuation of therapy. Upon cessation of treatment duloxetina the dose should be gradually reduced over 1-2 weeks in order to reduce the risk of developing the syndrome "cancel". If after reducing the dose or upon discontinuation of treatment, occur severe symptoms of the syndrome of "lifting", it may be considered continuing the previously assigned dose. Subsequently the physician may continue decreasing the dose, but even more gradually. Overdose Known cases of overdose with the simultaneous intake of up to 3000 mg of DULOXETINE as one, and in combination with other drugs. This is one of those cases ended in death. However, spontaneous (postmarketing) reports included descriptions of fatal acute overdose usually combined with taking a few drugs in which the dose of DULOXETINE was not more than 1000 mg. The symptoms (isolated or combined overdose): somnolence, coma, clonic convulsions, serotonin syndrome, vomiting and tachycardia. In preclinical studies (in animals) the main signs of toxicity associated with overdose, refers to disorders of the Central nervous system and the digestive system and include such symptoms as tremors, clonic convulsions, ataxia, vomiting and loss of appetite. Treatment: no specific antidote is known, however, in the case of development of serotonin syndrome may correctional treatment ciprogeptadina and application of methods of normalization of body temperature. Should ensure sufficient supply of fresh air. It is recommended to monitor cardiac activity and to monitor vital signs, along with symptomatic and supportive treatment. Gastric lavage may be indicated in that case, if too little time has passed since the ingestion, or in symptomatic treatment. In order to limit suction may be applied activated carbon. DULOXETINE is characterized by a large volume of distribution, the efficiency of forced diuresis, hemoperfusion, exchange perfusion, is questionable.



Drug interactions The monoamine oxidase inhibitors (MAOIS). Due to the risk of serotonin syndrome DULOXETINE should not be used in combination with MAOIS and within at least 14 days after stopping MAOI. Based on the half-life of DULOXETINE, you should take a break, at least 5 days after administration of DULOXETINE before taking MAOI. For selective MAOIS reversible action, such as moclobemide, the risk of serotonin syndrome below. However, the combined use of MAOIS reversible action and DULOXETINE is not recommended. Inhibitors of isoenzyme CYP1A2. Due to the fact that the isoenzyme CYP1A2 is involved in DULOXETINE metabolism, concomitant use of DULOXETINE with potential inhibitors of isoenzyme CYP1A2 is likely to lead to higher concentrations of DULOXETINE. Powerful inhibitor of the isoenzyme CYP1A2 fluvoxamine (100 mg 1 times/day) reduced the average plasma clearance of DULOXETINE by about 77%. Caution should be exercised when prescribing DULOXETINE with inhibitors of isoenzyme CYP1A2 (for example, some of quinoline antibiotics) and use smaller doses of DULOXETINE. Drugs affecting the Central nervous system. Caution should be exercised when DULOXETINE with other drugs and means influencing the Central nervous system, especially with those who have similar mechanism of action, including alcohol. Concomitant use with other drugs with serotonergic effects (for example, ISSN, SSRIs, triptana and tramadol) can lead to the development of serotonin syndrome. Serotonin syndrome. In rare cases, when coupled with the use of SSRIs (e.g. paroxetine, fluoxetine) and serotonergic drugs was observed serotonin syndrome. Care must be taken when using DULOXETINE together with serotonergic antidepressants such as SSRIs, tricyclic antidepressants (clomipramine or amitriptyline), St. John's wort, venlafaxine or triptan, tramadol, findin and tryptophan. The drugs that are metabolized by the isoenzyme CYP1A2. The simultaneous use of DULOXETINE (60 mg 2 times/day) had no significant effect on the pharmacokinetics of theophylline is metabolized by the isoenzyme CYP1A2. DULOXETINE is unlikely to have clinically significant effects on the metabolism of substrates of the isoenzyme CYP1A2. Drugs that are metabolized by CYP2D6 isoenzyme. DULOXETINE is a moderate inhibitor of CYP2D6 isoenzyme. When taking DULOXETINE at a dose of 60 mg 2 times/day with a single reception dezipramina, a substrate of CYP2D6 isoenzyme, AUC dezipramina increases in 3 times. Coadministration of DULOXETINE (40 mg 2 times/day) increased the equilibrium concentration of tolterodine (2 mg, 2 times/day) by 71%, but had no effect on the pharmacokinetics of 5 - gidroksimetabolita. Thus, caution should be exercised when using DULOXETINE with drugs that are mainly metabolized by the system of the isoenzyme CYP2D6 and have a narrow therapeutic index. Inhibitors of CYP2D6 isoenzyme. Since the isoenzyme CYP2D6 is involved in DULOXETINE metabolism, concomitant use of DULOXETINE with potential inhibitors of isoenzyme CYP2D6 may result in increased concentrations of DULOXETINE. Paroxetine (20 mg 1 times/day) reduced the average clearance of DULOXETINE by about 37%. When DULOXETINE with inhibitors of CYP2D6 isoenzyme (such as SSRIs) should be used with caution. Oral contraceptives and other steroid drugs. The results of in vitro studies demonstrate that DULOXETINE does not induce the catalytic activity of the isoenzyme CYP3A. Specific studies of drug interactions in vivo was conducted. Anticoagulants and antithrombotic drugs. Due to the potential increased risk of bleeding associated with pharmacodynamic interactions, caution must be exercised when coupled with the use of DULOXETINE and anticoagulants or antithrombotic drugs. In addition, the joint use of DULOXETINE and warfarin increased the value of the MHO. Nevertheless,concomitant use of DULOXETINE and warfarin at steady-state conditions in healthy volunteers under clinical pharmacology studies revealed no clinically significant changes in the MHO indicator medium or changes in the pharmacokinetics of right - or left-handed isomer of warfarin. Antacids and H2 antagonists-histamine receptors. The combined use of DULOXETINE and aluminum - and magnesium-containing antacids, or DULOXETINE and famotidine had no significant effect on the degree of absorption of DULOXETINE when using a dose of 40 mg. Inducers of isoenzyme CYP1A2. Population pharmacokinetic analysis showed that compared to non-Smoking patients, patients who smoke, the concentration of DULOXETINE in the plasma is nearly 50% lower. Drugs that are highly bound to proteins in the blood. DULOXETINE is largely bound to plasma proteins (> 90%). Therefore, the appointment of DULOXETINE to a patient taking another drug that has a high degree of binding to plasma proteins, may lead to increased concentrations of free fractions of both drugs. Cases of seizures and tinnitus were also observed after treatment with DULOXETINE. 2 Orthostatic hypotension and syncope were observed especially at the beginning of treatment. 3 Cm. the section "Special instructions". 4 Cases of aggression and hostility was observed especially at the beginning of treatment DULOXETINE or after its completion. 5 Cases of suicidal thoughts or suicidal behavior were observed during therapy DULOXETINE or in the early period after completion of treatment. 6 the Estimated frequency of adverse reactions. Was not observed during clinical trials. 7 Also includes hemorrhagic diarrhea, bleeding from the lower GI tract, vomiting blood, hemorrhoidal bleeding, melena, rectal bleeding, peptic ulcer bleeding. Padania met more frequently in the elderly (?65 years). 9 Including pain in the upper and lower abdomen, the tension of the anterior abdominal wall, abdominal discomfort, and gastrointestinal pain. 10 Including inner trembling, restlessness, tension, agitation. 11 Including night waking, early morning awakening, difficulty falling asleep. 12 Including hypersomnia, sedation. Wicca asthenia. Wicca increase systolic BP, diastolic pressure, systolic hypertension, diastolic hypertension, essential hypertension, hypertension. Wicca anorexia. Wicca muscle rigidity. Wicca myalgia and neck pain. Wicca the hyperesthesia, hyperesthesia of the face, hyperesthesia the genital area, the paresthesia of the mouth, very rare (<0.01%) the feeling of electric shock (at the termination of therapy). 19 Including confusion. 20 Including nightmares. 21 Including lack of ejaculation. 22 No statistically significant differences with placebo. Cancel DULOXETINE (especially simultaneously) often leads to a syndrome of "lifting" that includes the following symptoms: dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and vivid dreams), weakness, somnolence, agitation or anxiety, nausea and/or vomiting, tremor, headache, irritability, diarrhea, hyperhidrosis and vertigo. Overall, when taking selective inhibitors of serotonin reuptake (SSRI) and inhibitors of reuptake of serotonin and norepinephrine (ISSN), these effects are mild or moderate severity and limited in nature. However, in some patients, these effects may be more severe and/or prolonged. For this reason, if you cancel DULOXETINE recommended a gradual reduction in dose. With a short intake of DULOXETINE (up to 12 weeks) in patients with a painful form of diabetic peripheral neuropathy was observed a slight increase in the fasting blood glucose on the background of maintaining a stable concentration of glycosylated hemoglobin as taking DULOXETINE and the placebo group. When long-term therapy with DULOXETINE (up to 52 weeks) there was some increase in the concentration of glycosylated hemoglobin, which is 0.3% exceeded the increase of the respective indicator in patients receiving other treatment. In relation to the concentration of fasting glucose and total cholesterol in the blood in patients taking DULOXETINE, there was a slight increase in these parameters compared with a slight decrease observed in the control group patients. Corrected (relative HR) value of QT interval in patients taking DULOXETINE did not differ from that in the placebo group. Clinically significant differences between the indices of QT intervals, PR, QRS, or QTcB in the group of patients taking DULOXETINE and the placebo group was not.



Because coadministration of the drug with alcohol can have an effect similar to the effect of disulfiram (hot flashes, vomiting, tachycardia), you should warn patients that during the treatment Flagellum should not consume alcoholic beverages or medications containing alcohol. The long-term administration of the preparation is preferably carried out under the control of the blood formula. Leukopenia the possibility of further treatment depends on the risk of development of infectious process. In the treatment of Trichomonas vaginitis in women and Trichomonas urethritis in men should refrain from sexual activity. Necessarily simultaneous treatment of sexual partners. Treatment does not stop during menstruation. After therapy for trichomoniasis should conduct a control sample for 3 regular cycles before and after menstruation. After the treatment of giardiasis, if symptoms persist, after 3-4 weeks to spend 3 analysis of feces at intervals of several days (some successfully treated patients with lactose intolerance, caused by infestation may persist for several weeks or months, reminding the symptoms of giardiasis). Should discontinue treatment with the appearance of ataxia, dizziness, hallucinations, worsening of the neurological status of patients. You must take into account that metronidazole can be immobilized Treponema, which leads to false-positive test Nelson. Effects on ability to drive vehicles and management mechanisms In connection with the possibility of dizziness and other side effects associated with taking the drug, it is recommended to refrain from driving and other mechanisms. When kidney functions When expressed violations kidney (KK less 10 ml/min) is recommended to reduce the daily dose in 2 times.The terms and conditions of storage List B. the Drug should be kept out of the reach of children at a temperature from 15 to 30C. shelf Life 3 years. Do not use after expiry date. Readings depression; painful form of diabetic neuropathy; generalized anxiety disorder; chronic pain syndrome of the musculoskeletal system (including those caused by fibromyalgia, chronic pain in lower back pain and in osteoarthritis of the knee joint). Contraindications hypersensitivity to the drug components; concomitant use with MAO inhibitors; uncompensated angle-closure glaucoma; children up to age 18; sucrase/isomaltase deficiency, fructose intolerance, glucose-galactosemia malabsorption; liver disease, liver failure accompanied; concurrent administration of potent inhibitors of isoenzyme CYP1A2 (fluvoxamine, ciprofloxacin, enoxacin); severe chronic renal failure (KK less 30 ml/min); uncontrolled hypertension; children up to age 18; Tablets sublingual tablets for use under the tongue. Vaginal tablets (for vaginal suppositories extruded) tablets for vaginal insertion is obtained by pressing the granulated powder, which is processed fatty suppository mass. For the best introduction may have a thin lipid membrane. In addition to vaginal have been used and extruded urethral and rectal dosage forms. Tablets implantable (tablets depo, implant) is a sterile slow release tablets, in the form of very small disc or cylinder for implantation under the skin. The effervescent tablets uncoated tablets generally containing acid substances and carbonates or bicarbonates, which react quickly in water with the release of carbon dioxide; they are intended for dissolving or dispersing the drug in water immediately before taking. Homeopathic pills tablets, oral, obtained by pressing of triturate homeopathic, the weight of which in a single tablet is usually from 0.1 to 0.25 g. Tablets drops tablets for the preparation of drops. Pills for pasta pills for cooking pasta. Tablet for solution (soluble tablets) tablets for solution. Indicates the specific route of administration. Tablet for solution injection must be sterile. Pills pediatric pills sweet taste, used in pediatric practice. Method for preparing tablets are divided into two types: extruded tablets and pills trituratsionnye. Increase in blood pressure. In a few cases noted the rise in blood pressure during treatment with DULOXETINE. In patients with arterial hypertension and/or other cardiovascular diseases is recommended that blood pressure measurement. The liver or kidneys. In patients with severe impaired renal function (QC<30 ml/min) or severe hepatic insufficiency, there is an increase in the concentration of DULOXETINE in the plasma. If such patients receiving DULOXETINE clinically justified, you should use a lower initial dose of the drug. Suicidal behavior. The risk of suicide exists in all patients with depression and certain other mental disorders. This risk may persist until remission. As a consequence, patients in whom the risk of suicide is highest, should pharmacotherapy be under careful medical supervision. As well as taking other medications with similar duloxetina the mechanism of the pharmacological action (SSRIs, ISSN), the reception of DULOXETINE in the treatment process, or when to end it in some cases was associated with the development of suicidal thoughts and suicidal behavior. The use of DULOXETINE in patients under 18 years of age were not studied, and this drug is not intended for use in these patients. A causal relationship between administration of DULOXETINE and the occurrence of suicidal events in patients in this age group is not established. At the same time, some analytical reviews of results of several studies with the use of antidepressants for the treatment of mental disorders indicate an increased risk of suicidal ideation and/or suicidal behavior in children, adolescents and adults younger than 25 years compared with placebo. Doctors should encourage patients at any time to report all the troubling thoughts and feelings.



Increased risk of bleeding. SSRIs and ISSN, including DULOXETINE, may increase the risk of bleeding, including gastrointestinal. Therefore, DULOXETINE should be used with caution in patients taking anticoagulants and/or medicinal products that affect platelet function (e.g. NSAIDs, acetylsalicylic acid) and patients with a tendency to bleeding disorder. Hyponatremia. Very rarely reported cases of hyponatremia (in some cases, the content of serum sodium lower than 110 mmol/l). The majority of these cases occurred in elderly patients, especially in combination with altered fluid balance in recent history or in the presence of conditions predisposing to changes in fluid balance. Hyponatremia can manifest in the form of nonspecific symptoms (such as dizziness, weakness, nausea, vomiting, confusion, drowsiness, lethargy). The signs and symptoms, manifested in more severe cases, included fainting, falling, and seizures. Tablets divisible tablets with a diameter of more than 9 mm with one or two perpendicular to each other risks (scoring) that allows you to split the tablet into two or four parts and thus to vary the dosage of the medicine. Of crushed tablets tablets for the preparation of a solution or suspension requiring prior crushing. Covered and uncovered contain special excipients or received by a special technology that allows you to program the rate or place of release of medicinal substances. Tablets film coated tablets of one or more layers of auxiliary substances of natural or synthetic origin, sometimes with the addition of substances which have drug coverage or surfactants. Depending on the composition and method of application are distinguished coating: sugar-coated, film, extruded; depending on the environment in which to dissolve the coating: gastrosoluble (soluble in the stomach) and enteric (enteric-coated). The enteric-coated tablets (tablets gastro-resistant) tablets resistant to gastric juice and release the medicinal substance or substances in the intestinal juice. Is produced by coating tablets gastro-resistant shell (enteric-coated tablets) or by compressing granules and particles pre-coated gastro-resistant membrane or compaction of pharmaceutical substances in a mixture with gastro-resistant filler (Guruli). Coated tablets, film tablets, coated with a thin shell (film) of less than 10 % by weight of the tablet. The coating film may be soluble in water (from solutions of natural cellulose, polyethylene glycols, gelatin and gum Arabic, etc.) and insoluble in water, or varnish (some macromolecular compounds) Tablets, modified release coated or uncoated tablets that contain special excipients or received by a special technology that allows you to program the rate or place of release of medicinal substances. The term is used to refer to tablets with controlled-release tablets sustained release, tablets with the gradual release, etc. the Term is not used to name the pills are referred to as tablets depo, pills implantable, tablet retard tablets retard rapid. Tablet retard tablets with prolonged (periodic) release of the drug substance from the stock. Usually consist of microspheres with the drug substance, surrounded by a biopolymer matrix (base); layers dissolve the Foundation or microspheres, releasing another batch of the drug substance. Increased activity of hepatic enzymes. Some patients taking DULOXETINE in clinical studies, it was observed an increase in the activity of liver enzymes. The observed deviations were, as a rule, temporary and disappear spontaneously, or after discontinuation of DULOXETINE. A serious increase in the activity of liver enzymes (10 times or more greater than ULN) and liver damage cholestatic or mixed origin were rare, and in some cases have been associated with excessive alcohol use, or previous hepatic disease. Recommended be wary of DULOXETINE in patients who consume alcohol in large quantities, as well as with existing liver disease. Effects on ability to drive vehicles and management mechanisms In patients receiving DULOXETINE may experience sedation, drowsiness and other side effects. In this regard, patients receiving DULOXETINE, caution should be exercised in the management of hazardous mechanical means, including by car. When kidney functions To use caution in renal failure (QC 30-60 ml/min). When human liver To use caution if impaired liver.