2010/06/15

Plavix

Composition, structure and packing

Tablets, film-coated pink, round, slightly convex, engraved with "75" on one side and "1171" - on the other, the core tablets are white. 1 tab. clopidogrel hydrosulfate 97,875 mg, which is equivalent to the contents of clopidogrel 75 mg base .. Excipients: mannitol, macrogol 6000, microcrystalline cellulose (low water content, 90 microns), hydrogenated castor oil, gipromelloza nizkozameschennaya. The composition of the shell: Opadry 32K14834 (lactose, gipromelloza, triacetin, titanium dioxide, iron oxide red), carnauba wax.

Clinico-pharmacological group: antiagrigant.

Pharmacological action

Inhibition of platelet aggregation. Clopidogrel (or more precisely its active metabolite) irreversibly binds to the platelet ADP receptors (adenosine receptors) and selectively inhibits the binding of ADP to the ADP receptors of platelets and subsequent activation of the complex GPIIb / IIIa under the influence of ADP, thus inhibited ADP-induced platelet aggregation. Clopidogrel also inhibits platelet aggregation induced by other agonists, due to the fact that blocks the activation of platelets freed as ADP. Clopidogrel irreversibly binds to ADP-receptor inhibitors.

Consequently, platelets, which came to him in the interaction, immune to the stimulation of ADP during the entire period of their lives, and normal platelet function is restored with the same speed as renovation of platelets. Clopidogrel is capable of preventing the development of atherothrombosis in all localizations of atherosclerosis, particularly in lesions of cerebral, coronary or peripheral arteries.

With daily administration of clopidogrel 75 mg on the first day of admission showed a significant inhibition of ADP-induced platelet aggregation, which is gradually increased for 3-7 days and then goes to a constant level (when reaching the equilibrium state). In equilibrium, platelet aggregation is suppressed on average by 40-60%. After discontinuation of clopidogrel, platelet aggregation and bleeding time returned to its original level within an average of 5 days.

Pharmacokinetics

The absorption and distribution

During the regular ingestion Plavix 75 mg / day clopidogrel quickly absorbiruetsya.Ishodya from data on the removal of clopidogrel metabolite in urine, the absorption of clopidogrel is at least 50%. However, its concentration in blood plasma is negligible, and 2 h after administration does not reach the measurement limit (0.25 mg / l). Clopidogrel and the main metabolite is reversibly bound to plasma proteins (98% and 94% respectively), this relationship is unsaturated in a wide range of concentrations.

Metabolism

Clopidogrel is a prodrug and quickly biotransformiruetsya in the liver. Its active metabolite, thiol derivative, is formed by oxidation of clopidogrel in a 2-oxo-clopidogrel and subsequent hydrolysis. The oxidation process is governed primarily isoenzymes CYP2B6 and CYP3A4, and to a lesser extent - CYP1A1, 1A2, and 1S19.

Active thiol metabolite binds rapidly and irreversibly to platelet receptors, thus inhibiting platelet aggregation. This metabolite in plasma is not detected. The main metabolite of clopidogrel, (carboxyl derivative), is about 85% of circulating plasma metabolites of clopidogrel and has no pharmacological activity, but it is capable in vitro to inhibit the activity of 2C9 isoenzyme family of cytochrome P450. Cmax of the metabolite in blood plasma after repeated receptions Plavix 75 mg is about 3 mg / L and observed after approximately 1 h after administration.

The pharmacokinetics of the major metabolite is linear (plasma concentrations increase in proportion to dose) Clopidogrel in the dose range from 50 to 150 mg.

Withdrawal

Within 120 h after ingestion by man 14C-labeled clopidogrel about 50% of radiolabel excreted in the urine and approximately 46% - with the feces. T1 / 2 in the main circulating metabolite was 8 hours after single and repeated receptions.

Pharmacokinetics in special clinical situations

Concentrations of the main circulating metabolite in plasma with regular admission at a dose of 75 mg / day were lower in patients with renal failure severe (CC 5-15 ml / min) compared with patients with renal insufficiency moderately (CC 30-60 ml / min) and healthy volunteers. Although the inhibitory effect on ADP-induced platelet aggregation was reduced (25%) compared with the same effect in healthy volunteers, bleeding time was lengthened to the same extent as in healthy volunteers, PLAVIX 75 mg / day.

Clinical tolerability of clopidogrel in patients with renal failure did not differ from that in healthy individuals. In patients with liver cirrhosis (class A or B on the scale of Child-Pugh) daily for 10 days of receiving clopidogrel 75 mg / day was safe and well-tolerated, as well as in healthy individuals.

In patients with liver cirrhosis (class A or B on the scale of Child-Pugh) Cmax clopidogrel after the single dose and Cssmax clopidogrel after taking regular doses of the drug against the course of treatment were many times higher than in patients without cirrhosis. However, Cmax main circulating metabolite in the blood and the degree of suppression of clopidogrel ADP-induced aggregation of platelets, and bleeding time in patients with cirrhosis and without it were comparable.

Statement

Preventing atherothrombotic events in patients with myocardial infarction, ischemic insultomili diagnosed with occlusive disease of the peripheral arteries.

Preventing atherothrombotic events (in combination with acetylsalicylic acid) in patients with acute coronary syndrome:
without ST segment elevation ST (unstable angina or myocardial infarction without teeth Q), including patients who underwent a stenting during percutaneous coronary intervention;
c-segment elevation ST (acute myocardial infarction) with medical treatment and the possibility of thrombolysis.

Dosage regimen

For the prevention of ischemic disorders in patients after myocardial infarction, ischemic stroke and diagnose peripheral arterial occlusive lesion adults (including elderly patients) designate 75 mg 1 time / day irrespective of food intake. Treatment should begin with the first days to 35 days after myocardial infarction and from 7 days to 6 months - after ischemic stroke.

In acute coronary syndrome without ST elevation ST (unstable angina or myocardial infarction without teeth Q) treatment should be started with the appointment of a single loading dose of 300 mg, and then continue to use the drug at a dose of 75 mg 1 time / day (with a simultaneous appointment of acetylsalicylic acid in a dose 75-325 mg / day). Since the use of acetylsalicylic acid in high doses is associated with greater risk of bleeding, the recommended dose should not exceed 100, the course of treatment - up to 1 year.

In acute myocardial infarction with ST-segment elevation medication prescribed at a dose of 75 mg of 1 times / day with initial loading dose in combination with acetylsalicylic acid in combination with or without thrombolytics. For patients aged over 75 years of clopidogrel treatment should be carried out without loading dose. Combination therapy begins as soon as possible after the onset of symptoms and continued for at least 4 weeks.

Side effect

Safety of clopidogrel has been studied in clinical trials of more than 42 000 patients, including over 9000 patients receiving the drug for a year or longer. Clinically important side effects observed in trials CAPRIE, CURE, CLARITY and COMMIT, are discussed below. Tolerability of clopidogrel in a dose of 75 mg / day in CAPRIE trial corresponded to the tolerance of acetylsalicylic acid in a dose of 325 mg / day. Overall tolerability was similar tolerability of acetylsalicylic acid, regardless of age, sex and race of patients. From the blood coagulation system: a test of CAPRIE - the overall frequency of bleeding in patients treated with clopidogrel or acetylsalicylic acid, was 9.3%, the frequency of severe cases in the application of clopidogrel was 1.4%, and the application of acetylsalicylic acid - 1.6%.

Patients who received clopidogrel, gastrointestinal bleeding occurred in 2.0% of cases, and in 0.7% of the cases required hospitalization.

In patients treated with acetylsalicylic acid, the corresponding rate was 2.7% and 1.1%. The frequency of other bleeding was higher in patients treated with clopidogrel, compared with acetylsalicylic acid (7.3 and 6.5% respectively). However, the frequency of severe cases was the same in both groups (0.6 and 0.4% respectively). The most frequently observed in both groups purpura / bruising / hematoma and epistaxis. Less frequent bruising, haematuria and eye bleeding (mainly conjunctival). The frequency of intracranial hemorrhage was 0.4% in patients treated with clopidogrel and 0.5% in patients treated with acetylsalicylic acid.

In a trial CURE - use a combination of clopidogrel + aspirin compared with placebo + combination of acetylsalicylic acid does not lead to a statistically significant increase in life-threatening bleeding (frequency of 2.2% compared to 1.8%) or fatal bleeding (frequency of 0.2% compared to 0.2% respectively), but the risk of large, small and other bleeding was significantly higher when using a combination of clopidogrel + aspirin: major bleeding, do not pose danger to life (1.6% - clopidogrel + aspirin, 1.0% - placebo + aspirin), primarily gastrointestinal bleeding and bleeding at the injection site, as well as small bleeding (5.1% - clopidogrel + aspirin, 2.4% - placebo + aspirin). The frequency of intracranial bleeding in both groups was 0.1%.

The frequency of major bleeding when using a combination of clopidogrel + aspirin depended on the dose of the latter (<100> 200 mg: 4.9%), as well as the application of a combination of aspirin with placebo (≤ 100 mg: 2.0%; 100-200 mg: 2.3%> 200 mg: 4.0%). During the test, the risk of bleeding (life-threatening, large, small, other) decreased: 0-1 months [clopidogrel: 599/6259 (9.6%), placebo: 413/6303 (6.6%)], 1-3 months [ clopidogrel: 276/6123 (4.5%), placebo: 144/6168 (2.3%)], 3-6 months [clopidogrel: 228/6037 (3.8%), placebo: 99/6048 (1.6%)], 6-9 months [clopidogrel: 162/5005 (3.2%), placebo: 74/4972 (1.5%)], 9-12 months [clopidogrel: 73/3841 (1.9%), placebo: 40/3844 (1.0%)].

In patients who have stopped taking the drug for more than 5 days before coronary artery bypass surgery, there was no increase in the frequency of major bleeding within 7 days after surgery for coronary bypass surgery (4.4% in the clopidogrel + aspirin and 5.3% for placebo + aspirin). In patients who continued taking the drug for five days prior to coronary bypass surgery, the frequency was 9.6% in the clopidogrel + aspirin and 6.3% - in the case of placebo + aspirin.

In the CLARITY trial observed a general increase in the frequency of bleeding in the group of clopidogrel + aspirin (17.4%) compared with placebo + aspirin (12.9%). The frequency of major bleeding were similar in both gpyppax (1.3% and 1.1% in gpyppax clopidogrel + aspirin and placebo + aspirin, respectively). This value was sustained in all subgroups of patients defined by the underlying characteristics and type of fibrinolytic and heparin therapy.

The frequency of fatal bleeding (0.8% and 0.6% in the clopidogrel + aspirin and placebo + aspirin, respectively) and intracranial hemorrhage (0.5% and 0.7% in the clopidogrel + aspirin and placebo + aspirin, respectively) was low and similar in both gpyppax. In the COMMIT trial the overall frequency of major bleeding netserebralnyh or cerebral bleeding was low and similar in both groups (0.6% and 0.5% in the clopidogrel + aspirin and placebo + aspirin, respectively). On the part of the hemopoietic system: a test CAPRIE - severe neutropenia (<0.45h109 / l) was observed in 4 patients (0.04%) treated with clopidogrel and 2 patients (0.02%) treated with acetylsalicylic acid.

In 2 patients from 9599 who received clopidogrel, the number of neutrophils was zero, and none of 9586, receiving acetylsalicylic acid, such values are not observed. In the course of clopidogrel treatment was observed one case of aplastic anemia.

Frequency of severe trombopitopenii (<80> 1 / 100, <1> 1 / 1000, <1> 1 / 10000, <1 / 1000). Within each group the frequency of side effects is presented in order of decreasing severity.
From the central nervous system and peripheral nervous system: sometimes - headache, dizziness, paresthesias, rare - vertigo.
On the part of the digestive system: often - dyspepsia, diarrhea, abdominal pain, sometimes - nausea, gastritis, flatulence, constipation, vomiting, stomach ulcer and duodenal ulcer.
From the blood coagulation system: sometimes - lengthening the time of bleeding.
On the part of the hemopoietic system: sometimes - leukopenia, reducing the number of neutrophils and eosinophils, reducing the number of platelets. Dermatological reactions: sometimes - a rash and itching.

Post marketing surveillance data
From the blood coagulation system: the most common - hemorrhage (in most cases - during the first month of treatment). There are several fatal cases (intracranial, gastrointestinal and retroperitoneal bleeding), there are reports of severe cases of skin bleeding (purpura), musculoskeletal bleeding (Hemarthrosis, hematoma), ocular hemorrhages (conjunctival, ocular, retinal), epistaxis , hemoptysis, pulmonary hemorrhage, hematuria, and bleeding from the wound, the patients taking clopidogrel simultaneously with acetylsalicylic acid or acetylsalicylic acid and heparin, have also been cases of severe bleeding.

In addition to these clinical trials were spontaneously declared the following side effects. In each class of bodies (classification MedDRA), they are showing the frequency. The term "very rare" corresponds to a frequency <1 / 10000. Within each group the frequency of side effects is presented in order of decreasing severity.
On the part of the hemopoietic system: very rarely - thrombocytopenic purpura trombogemoliticheskaya (1 in 200 000 patients), severe thrombocytopenia (platelet count ≤ 30 000/mkl), granulocytopenia, agranulocytosis, anemia, and aplastic anemia / pancytopenia.
From the side of the central nervous system: very rarely - confusion, hallucinations.
Since the cardiovascular system: a very rare - vasculitis, hypotension.
On the part of the respiratory system: very rarely - bronchospasm, interstitial pneumonitis.
On the part of the digestive system: very rarely - colitis (including ulcerative colitis or lymphocytic), pancreatitis, changes in taste, stomatitis, hepatitis, acute liver failure, increase in liver enzymes.
On the part of the musculoskeletal system: very rarely - arthralgia, arthritis, myalgia.
From the urinary system: very rarely - glomerulonephritis, increased blood creatinine. Dermatological reactions: very rare - Bullous rash (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), erythematous rash (associated with clopidogrel or acetylsalicylic acid), eczema, shingles, flat. Allergic reactions: seldom - angioedema, urticaria, anaphylactoid reactions, serum sickness. Other: very rarely - fever.

Contraindications
severe hepatic insufficiency.
acute pathological bleeding such as bleeding ulcers izpepticheskoy vnutricherepnoekrovoizliyanie.
a rare hereditary galactose intolerance, lactase deficiency syndrome and glucose-galactose malabsorption.
Pregnancy
Lactation (breastfeeding).
Children age 18 years (safety and efficacy not established);
Hypersensitivity to the drug's components.

Be wary prescribers with moderate hepatic insufficiency, in which the possible predisposition to bleeding (limited clinical experience with) renal impairment (limited clinical experience using) for injuries, surgical procedures, the diseases for which there is a predisposition to the development of bleeding (especially gastrointestinal -intestinal or intraocular), while taking NSAIDs, including selective COX-2 inhibitor, while the appointment of warfarin, heparin, inhibitors of glycoprotein IIb / IIIa.

Precautions should be prescribed the drug for liver and kidney (including at moderate hepatic and / or renal insufficiency), trauma, preoperative states.

Pregnancy and lactation

Given the lack of data is not advisable to appoint Plavix during pregnancy and lactation (breastfeeding). In experimental studies did not establish any direct or indirect adverse effects on pregnancy, fetal development, childbirth and postnatal development. In studies on rats have shown that clopidogrel and / or its metabolites are excreted with breast milk.

It is not known whether clopidogrel is allocated with breast milk in humans.

Application for violations of liver function

Precautions should be prescribed the drug to treat liver diseases (including those with moderate hepatic insufficiency). Do not use this with hepatic failure and severe.

Application for violations of renal function

Precautions should be prescribed a drug for kidney (including renal failure of moderate degree).

Cautions

When using Plavix, especially during the first weeks of treatment and / or after invasive cardiac procedures / surgery, it is necessary to closely monitor patients for signs of bleeding exceptions, including hidden.

Because of the risk of bleeding and haematological side effects in case of a course of treatment of clinical symptoms suspicious for bleeding, should urgently make clinical blood test to determine APTT, platelet count, indicators of functional activity of platelets and conduct other necessary investigations.

Plavix, as well as other antiplatelet drugs should be used with caution in patients with increased risk of bleeding associated with trauma, surgery or other pathological conditions as well as combination therapy with acetylsalicylic acid, NSAIDs (including inhibitors COX-2), heparin or inhibitors of glycoprotein IIb / IIIa. Combined use of clopidogrel with warfarin may increase bleeding, so, except in rare clinical situations (such as the presence of floating thrombus in the left ventricle, stenting in patients with atrial fibrillation), the combined use of Plavix, and warfarin is not recommended.

With the planned surgical treatment Plavix should be discontinued 7 days before surgery. Clopidogrel should be used with caution in patients with the risk of bleeding (particularly gastrointestinal and intraocular).

Patients should be warned that while taking Plavix (alone or in combination with acetylsalicylic acid) to stop the bleeding may require more time, and that in case they have an unusual (for containment or duration) of bleeding, they should inform about your doctor. Before any of the forthcoming operation and before taking any new drug patients should inform the doctor (including dental) for the admission of clopidogrel. There were also cases of thrombotic thrombocytopenic purpura (TTP) after administration of clopidogrel. It is characterized by thrombocytopenia and microangiopathic hemolytic anemia in combination with any neurological symptoms, impaired renal function or fever.

Development of TTP may be life-threatening and require urgent action, including plasmapheresis. Because of insufficient data clopidogrel should not be given in acute ischemic stroke (in the first 7 days). The drug should be prescribed with caution in patients with impaired renal function. In the period of treatment necessary to control the functional activity of the liver.

In severe liver disease should be aware of the risk of hemorrhagic diathesis. Patients with congenital intolerance galactose malabsorption syndrome, glucose-galaktazy and lactase deficiency should not be given Plavix.

Effects on ability to driving and management mechanisms

No signs of deterioration in the ability of driving a car or reduce mental performance after taking Plavix found.

Overdose

Symptoms: Extension of time of bleeding and subsequent complications in the form of bleeding. Treatment: If you experience bleeding should be carried out appropriate therapy. If you need quick correction lengthens bleeding time, platelet transfusion is recommended. No specific antidote.

Drug Interactions

Combined use of clopidogrel with warfarin is not recommended because this combination can increase the intensity of bleeding. Appointment of inhibitors of glycoprotein IIb / IIIa with Plavix requires caution. Acetylsalicylic acid does not alter the inhibitory effect of Plavix on ADP-induced platelet aggregation, but enhances the effect of Plavix aspirin on collagen-induced platelet aggregation. The combined use of these drugs requires caution. However, in acute coronary syndrome without ST segment elevation is recommended for a long joint use of Plavix and aspirin (up to 1 year). When applied simultaneously with heparin, according to a clinical trial conducted in healthy volunteers, Plavix did not alter either the overall need for heparin, or the effect of heparin on blood coagulation.

The simultaneous use of heparin did not alter the inhibitory effect of Plavix on platelet aggregation. However, the safety of such combinations has not yet been established, and the simultaneous use of these drugs requires caution.

Safety joint for clopidogrel, fibrin-specific and fibrin-nonspecific thrombolytic agents and heparin was investigated in patients with acute myocardial infarction. The frequency of clinically significant bleeding was similar to that observed in the case of joint use of thrombolytic drugs and heparin with acetylsalicylic acid. Appointment of NSAIDs (including COX-2 inhibitor), together with Plavix requires caution.

In a clinical study involving healthy volunteers, the combined use of clopidogrel and naproxen increased the hidden loss of blood through the digestive tract. However, due to the lack of research on the interaction of clopidogrel with other NSAIDs is not currently known whether there is an increased risk of gastrointestinal bleeding when taking clopidogrel with other NSAIDs. A number of clinical studies with clopidogrel and other drugs at the same time appointed to examine the possible pharmacodynamic and pharmacokinetic interactions, which showed the following.

Clopidogrel with atenolol, nifedipine, or both drugs simultaneously clinically significant pharmacodynamic interactions were observed (according to clinical studies to examine the possible pharmacodynamic and pharmacokinetic interactions). The simultaneous use of phenobarbital, cimetidine, and estrogen had no significant effect on the pharmacodynamics clopidogrel (based on clinical studies to examine the possible pharmacodynamic and pharmacokinetic interactions).

Pharmacokinetic parameters of digoxin and theophylline did not change at their joint application to clopidogrel (based on clinical studies to examine the possible pharmacodynamic and pharmacokinetic interactions). Antacid not reduce absorption clopidogrel (according to clinical studies to examine the possible pharmacodynamic and pharmacokinetic interactions).

Phenytoin and tolbutamide may be safety used in conjunction with clopidogrel (study CAPRIE), despite the fact that the data obtained in studies with human liver microsomes indicate that the carboxyl metabolite of clopidogrel could inhibit the activity of the 2C9 isoenzyme of cytochrome P450 family, which may lead to an increase of plasma concentrations of certain drugs (phenytoin, tolbutamide and certain NSAIDs), which are metabolized by 2C9 isoenzyme family of cytochrome P450.

In clinical studies found no clinically significant adverse interactions clopidogrel with ACE inhibitors, diuretics, β-blockers, calcium channel blockers, lipid-lowering drugs, coronary vasodilators, antidiabetic agents (including insulin), antiepileptic drugs, hormone replacement therapy and antagonist GPIIb / IIIa.

Terms and Conditions of storage

List B. The drug should be stored out of reach of children at or above 30 ° C. Shelf life - 3 years.

Avelox

Composition, structure and packing

Coated tablets pink color, matte, oblong, convex, with napechatkoy as a trademark "BAYER" on one side and "M400" - from the back, on the break - a homogeneous mass of white to light yellow to greenish color, surrounded by membrane shell pink.

1 tab. moxifloxacin hydrochloride 436.8 mg, which corresponds to the content of moxifloxacin 400 mg.

Excipients: lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, magnesium stearate, gipromelloza, iron oxide red, macrogol 4000, titanium dioxide. Solution for infusion transparent, greenish-yellow color.

1 vial. moxifloxacin hydrochloride 436 mg, which corresponds to the content of moxifloxacin 400 mg.

Excipients: sodium chloride, sodium hydroxide, hydrochloric acid, water d / and.

Clinico-pharmacological group: antibacterial fluoroquinolones Group.

Pharmacological action

Antibacterial fluoroquinolone group. Bactericidal action. The mechanism of action due to the inhibition of bacterial topoisomerases II and IV, which leads to disruption of DNA synthesis of microbial cells. In vitro drug is active against a broad spectrum of gram-negative and gram-positive bacteria, mycoplasmas, chlamydia, ureaplasma, Legionella, anaerobic pathogens. Effective against bacteria resistant to beta-lactam and macrolide antibiotics.

By Avelox susceptible Gram-positive aerobic bacteria: Streptococcus pneumoniae (including strains resistant to penicillin and macrolides), Streptococcus pyogenes (group A), Streptococcus milled, Streptococcus mitis, Streptococcus agalactiae, Streptococcus dysgalactiae, Staphylococcus aureus (including methicillin-sensitive strains), Staphylococcus cohnii, Staphylococcus epidermidis (including methicillin-sensitive strains), Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus simulans, Corynebacterium diphtheriae; Gram-negative aerobic bacteria: Haemophilus influenzae (including strains producing and β-lactamases neprodutsiruyuschie), Haemophilus parainfluenzae, Klebsiella pneumoniae , Moraxella catarrhalis (including producing strains and β-lactamases neprodutsiruyuschie), Escherichia coli, Enterobacter cloacae, Bordetella pertussis, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter intermedius, Enterobacter sakazaki, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri , Providencia stuartii;

anaerobic bacteria: Bacteroides distasonis, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Fusobacterium spp., Porphyromonas spp. (Including Porphyromonas anaerobius, Porphyromonas asaccharolyticus, Porphyromonas magnus), Prevotella spp., Propionibacterium spp., Clostridium perfringens, Clostridium ramosum; and Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila, Coxiella burnettii.

Moxifloxacin less active against Pseudomonas aeruginosa, Pseudomonas fluorescens, Burkholderia cepacia, Stenotrophomonas maltophilia.

The mechanisms leading to the development of resistance to penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines, do not violate the antibacterial activity of moxifloxacin. Cross-resistance between these two groups of antibacterial drugs and moxifloxacin is not indicated. The overall incidence of resistance is very low (10-7-10-10).

Resistance to moxifloxacin develops slowly by multiple mutations.

There are cases of cross-resistance to quinolones. Nevertheless, some resistant to other quinolones and gram-positive anaerobic organisms are susceptible to moxifloxacin.

Pharmacokinetics

Absorption

Following oral moxifloxacin is absorbed rapidly and almost completely. After a single dose of moxifloxacin in a dose of 400 mg Cmax in the blood is reached within 0.5-4 h and is 3.1 mg / liter. When receiving moxifloxacin with food had been a slight increase in the time to reach C max (2 h) and a slight decrease in C max (about 16%), while the duration of absorption is not changed. However, these data do not have clinical significance, and the drug can be applied regardless of the meal.

After a single infusion at a dose of Avelox 400 mg for 1 h Cmax is achieved at the end of infusion and was 4.1 mg / l, which corresponds to its increase by approximately 26% compared with the value of this index at intake. When multiple I / O infusions at a dose of 400 mg, duration 1 h Cmax varies from 4.1 mg / l to 5.9 mg / liter. Mean Css, equal to 4.4 mg / l, achieved at the end of infusion.

The absolute bioavailability of approximately 91%.

Distribution

Pharmacokinetics of moxifloxacin when receiving a dose of 50 to 1200 mg dose, and 600 mg / day for 10 days is linear. The equilibrium state is achieved within 3 days. Moxifloxacin rapidly distributed in tissues and organs and is associated with blood proteins (mainly albumin) by about 45%. Vd is approximately 2 l / kg. High concentrations of the drug exceed those in plasma, created in lung tissue (including the alveolar macrophages) in the mucosa of the bronchi, sinuses, soft tissue, skin and subcutaneous structures, foci of inflammation. In the interstitial fluid and saliva drug is determined in a free, not protein-bound form, in concentrations higher than in plasma.

Metabolism

Biotransformiruetsya to inactive sulfosoedineny and glucuronide. Moxifloxacin not Biotransformation microsomal liver enzyme cytochrome P450.

Withdrawal

Excreted in the urine and the faeces as unchanged, and in the form of inactive metabolites. Approximately 19% of a single dose (400 mg) is excreted unchanged in the urine, about 25% - with the feces. T1 / 2 of approximately 12 h. The average total clearance after taking a dose of 400 mg range from 179 to 246 ml / min.

Pharmacokinetics in special clinical situations

There is no difference in pharmacokinetic parameters of moxifloxacin, depending on age, sex and race. Studies of the pharmacokinetics of moxifloxacin in children has not been conducted. There were no significant changes in the pharmacokinetics of moxifloxacin in patients with impaired renal function (including at QA <30 ml/min/1.73 m2) and of those who are on hemodialysis and continuous ambulatory peritoneal dialysis prolonged. In patients with mild and moderate hepatic impairment (class A or B on the scale of Child-Pugh) pharmacokinetics of moxifloxacin is not changed. In patients with severely impaired liver function (class C according to Child-Pugh scale) data on the pharmacokinetics of moxifloxacin is not.

Statement

Infectious and inflammatory diseases in adults caused by microorganisms sensitive to the drug:
Acute sinusitis;
community-acquired pneumonia (including those caused by strains of microorganisms with multiple antibiotic resistance *);
exacerbation of chronic bronchitis;
uncomplicated infections of skin and soft tissues;
Complicated infections of skin and subcutaneous structures (including diabetic foot infection).

Streptococcus pneumoniae with multiple resistance to antibiotics including strains resistant to penicillin, and strains resistant to two or more antibiotics from groups such as penicillin (minimal inhibitory activity at ≥ 2 mg / ml), cephalosporins II generation (cefuroxim), macrolides, tetracyclines and trimethoprim / sulfamethoxazole.

Dosage regimen

The drug is prescribed in and in / 400 mg 1 time / day. The duration of treatment when administered in / in the introduction determined by the severity of infection and clinical effect and it is: during exacerbation of chronic bronchitis - 5 days, with pneumonia the total duration of the step therapy - 7-14 days, first in /, then inside, or 10 days inward with acute sinusitis and uncomplicated skin infections and soft tissue - 7 days for complicated infections of the skin and subcutaneous tissue - the total length of the step therapy Avelox (w / introduction, followed by oral administration) is 7-21 days.

Duration of treatment Avelox in / up to 14 days, inside - 21 days.

Elderly patients, patients with minor disturbances of liver function (class A or B on the scale of Child-Pugh), patients with impaired renal function (including spacecraft at <30 ml/min/1.73 m2), as well as patients who are on continuous hemodialysis and long-term ambulatory peritoneal dialysis, changes in dosage regimen is not required.

Tablets should be taken, not liquid, squeezed a small amount of water, regardless of the meal. The solution for infusion should be administered in / in slowly for 60 minutes. The drug can be entered in the diluted and undiluted. Avelox solution compatible with the following solutions: water for injection, sodium chloride 0.9% solution of sodium chloride, 1M, dextrose 5% Dextrose 10% Dextrose 40%, 20% xylitol solution, Ringer's solution, Ringer-lactate solution aminofuzina 10% solution yonosterila. You should use only clear solution.

Side effect
Since the cardiovascular system: <3% - long QT patients with concomitant hypokalemia; ≥ 0.1%, <1% - tachycardia, prolongation of the interval QT, arrhythmia; ≥ 0.01%, <0.1% - ventricular tachyarrhythmia, hypotension, hypertension, flushing of the face (due to vasodilation), <0.01% - polymorphic ventricular tachycardia (type "pirouette"), heart failure (predominantly in patients with predisposing to arrhythmia conditions such as clinically significant bradycardia, acute myocardial ischemia).
On the part of the digestive system: ≥ 1%, <10% - nausea, diarrhea, <3% - abdominal pain, vomiting, symptoms of dyspepsia, transient increase in transaminase activity; ≥ 0.1%, <1% - bloating, constipation, anorexia, gastroenteritis, increased activity of GGTP, amylase, bilirubin, transient abnormal liver function with increased LDH, transient increase in alkaline phosphatase; ≥ 0.01%, <0.1% - dysphagia, pseudomembranous colitis (in rare cases associated with life-threatening complications), jaundice, hepatitis ( predominantly cholestatic).
From the central nervous system and peripheral nervous system: <3% - dizziness, headache; ≥ 0.1%, <1% - disturbances of consciousness (confusion, disorientation), insomnia, dizziness, drowsiness, anxiety, tremor, paresthesia / dysesthesia, increased psychomotor activity; ≥ 0.01%, <0.1% - abnormal dreams, impaired coordination (including disorders of walking as a result of dizziness, in very rare cases, leading to injuries from a fall, especially in older patients), seizures with different clinical manifestations (including am grand mal seizures), violation of attention, speech disorders, amnesia, emotional lability, hallucinations, depression (in very rare cases, may conduct with a tendency to self-harm), hypoesthesia, <0.01% - hyperaesthesia, depersonalization, psychotic reactions (potentially manifest themselves in behavior with a tendency to self-harm). Adverse reactions associated with the chemotherapeutic effect of: <3% - moniliasis superinfection, including stomatitis, vagina.
The part of the hemopoietic system: ≥ 0.1%, <1% - anemia, leukopenia, thrombocytosis, thrombocytopenia, eosinophilia.
From the blood coagulation system: ≥ 0.01%, <0.1% - change in the content thromboplastin, increased prothrombin time / INR increased, <0.01% - increase in the level of prothrombin / decrease in MND.
On the part of the musculoskeletal system: ≥ 0.1%, <1% - arthralgia, myalgia; ≥ 0.01%, <0.1% - tendonitis, muscle cramps, <0.01% - tendon rupture, arthritis, gait disturbance due to side effects of the musculoskeletal system .
From the senses: ≥ 0.1%, <1% - disturbance of taste, blurred vision, reduced visual acuity, diplopia (especially in combination with dizziness and confusion); ≥ 0.01%, <0.1% - tinnitus, a violation of smell, including anosmia.
On the part of the respiratory system: ≥ 0.1%, <1% - shortness of breath, asthmatic condition.
On the part of metabolism: ≥ 0.1%, <1% - hyperhidrosis, degitratatsiya (caused by diarrhea or decrease in fluid intake), hyperlipidemia; ≥ 0.01%, <0.1% - hyperglycemia, hyperuricemia.
From the urinary system: ≥ 0.01%, <0.1% - renal failure as a result of dehydration, which can lead to kidney damage, especially in elderly patients with concomitant impaired renal function. Allergic reactions: ≥ 0.1%, <1% - urticaria, pruritus, rash; ≥ 0.01%, <0.1% - an anaphylactic reaction, anaphylactic shock (including life-threatening), angioedema (including swelling of face, throat, potentially life-threatening), <0.01% - Stevens-Johnson syndrome.

Other: ≥ 0.1%, <1% - asthenia, malaise; ≥ 0.01%, <0.1% - pelvic pain, swollen face, back pain, pain in the legs.

Contraindications
Pregnancy
lactation (breastfeeding);
childhood and adolescence to 18 years;
hypersensitivity to moxifloxacin and other components of the drug.

Precautions to apply for central nervous system diseases (including the diseases suspected in the involvement of the CNS) that predisposes to the appearance of seizures and lowers the threshold of convulsive readiness, while lengthening the interval QT, hypokalemia, bradycardia, acute myocardial ischemia, while admission to the drugs prolong the interval QT, and antiarrhythmics IA and III classes, with severe hepatic insufficiency.

Pregnancy and lactation

Safety of Avelox in pregnancy is not installed, so its use is contraindicated. A small amount of moxifloxacin is excreted in breast milk. Data on the use of moxifloxacin in women during lactation are absent. Therefore the use of Avelox in the period of breastfeeding is also contraindicated.

In the experimental investigations in studying the effect of moxifloxacin on the reproductive function in rats, rabbits and monkeys demonstrated that moxifloxacin penetrates the placental barrier. Studies in rats (with the introduction of moxifloxacin in and IV) and monkeys (with the introduction of moxifloxacin oral) did not reveal teratogenic action of moxifloxacin and its effects on fertility. When i / in the introduction of moxifloxacin in rabbits at a dose of 20 mg / kg were observed malformations of the skeleton. Revealed an increase in the number of miscarriages in monkeys and rabbits in the application of moxifloxacin in a therapeutic dose. Rats decreased fetal weight, increased miscarriages, a slight increase in the duration of pregnancy and an increase in spontaneous activity of offspring of both sexes in the application of moxifloxacin, the dose is 63 times higher than recommended.

Application for violations of liver function

Patients with minor disturbances of liver function (class A or B on the scale of Child-Pugh) changes in dosage regimen is not required.

With caution used in severe hepatic failure.

Application for violations of renal function

Patients with impaired renal function (including at QA <30 ml/min/1.73 m2), as well as patients who are on hemodialysis and continuous ambulatory peritoneal dialysis, long-term, changes in dosage regimen is not required

Cautions

Please note that the appointment of Avelox increases the risk of seizures, so carefully prescribed the drug to patients with diseases of the CNS, accompanied by seizures or predisposing to their development or reduce the threshold of convulsive readiness, as well as suspected of such diseases and conditions.

In the absence of sufficient clinical data use of moxifloxacin in patients with severely impaired liver function (class C according to Child-Pugh scale) is not recommended. During the treatment, fluoroquinolones, including moxifloxacin, especially in the elderly and patients receiving SCS may develop tendonitis and tendon rupture. If you have pain or signs of inflammation of the tendon, stop taking Avelox and unload the affected limb.

When using Avelox in some patients there may be lengthening the interval QT. In this regard, should avoid use of the drug to patients with prolonged interval QT, hypokalemia, and patients receiving antiarrhythmic drugs class IA (quinidine, procainamide) or class III (amiodarone, sotalol), since experience with moxifloxacin in these patients is limited. Caution appoint Avelox, along with drugs that prolong the interval QT (tsizaprid, erythromycin, antipsychotic drugs, tricyclic antidepressants), as well as in patients with predisposing to arrhythmia conditions such as bradycardia, acute myocardial ischemia. The degree of QT interval prolongation may increase with increasing concentration of the drug, so it should not exceed the recommended dose. Lengthening of QT interval associated with an increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia. None of the 8000 patients treated with moxifloxacin, were noted associated with prolonged QT cardiovascular complications and fatalities. However, patients with predisposing to arrhythmias states in the application of moxifloxacin may increase the risk of ventricular arrhythmias. Antibiotics pose a risk of pseudomembranous colitis. This should be borne in mind in the event during the treatment Avelox severe diarrhea. In this case, the drug should be repealed and immediately assign the appropriate therapy.

There is a risk of hypersensitivity reactions and anaphylactic reactions in the primary use of the drug, such cases should immediately inform your doctor. Very rare anaphylactic reaction can progress to anaphylactic shock. In such cases, you should immediately cease injection of the preparation and conduct appropriate resuscitation (including anti-shock).

In the application of quinolones marked photosensitivity reactions. However, during the pre-clinical, clinical research, as well as the application of Avelox in clinical practice was reported photosensitivity reactions. Nevertheless, patients in the period of drug administration should avoid direct sunlight or UV irradiation. Patients of different ethnic groups, dose adjustment is required.

Use in Pediatrics

Efficacy and safety of the drug Avelox in children and adolescents has not been established.

Effects on ability to driving and management mechanisms

Despite the fact that moxifloxacin rarely causes adverse reactions from the CNS, the possibility of driving or moving machinery solved individually after assessing the patient's response to receiving the drug.

Experimental Results

The following pathological changes are manifestations of the toxic effects of moxifloxacin, like other fluoroquinolones: a system of hematopoiesis (bone marrow hypoplasia in dogs and monkeys), CNS (convulsions in monkeys) and liver (increased liver enzymes, isolated necrosis of hepatocytes in rats, dogs and monkeys) . These violations occur, usually after a long period of administration of moxifloxacin in high doses.

Overdose

There have not been any side effects when applied at a dose of Avelox to 1200 mg dose and 600 mg for more than 10 days. Treatment: In case of overdose in accordance with the clinical situation hold symptomatically with ECG monitoring. Application of activated charcoal is advisable only when an overdose of moxifloxacin in tablet form.

Drug Interactions

Joint application inside Avelox and antacids, minerals and vitamin-mineral complexes can disrupt the absorption of moxifloxacin due to the formation of chelate complexes with polyvalent cations contained in these preparations, and consequently reduce the concentration of moxifloxacin in plasma. In this regard, Antacid, antriretrovirusnye and other preparations containing calcium, magnesium, aluminum, iron, should take at least 4 hours before or 2 hours after oral Avelox. Ranitidine, while applying slight changes absorption of moxifloxacin. When combined with the use of preparations containing calcium in high doses, clinically significant effect on the absorption of moxifloxacin were found except for a small reduction of the rate of absorption. When using Avelox with antiarrhythmic drugs class IA (quinidine, procainamide) or class III (amiodarone, sotalol), as well as drugs that prolong the interval QT (tsizaprid, erythromycin, antipsychotic drugs, tricyclic antidepressants) may be an additive effect on QT interval prolongation .

Moxifloxacin does not have any effect on the pharmacokinetics of theophylline (and vice versa), indicating that moxifloxacin does not interact with the CYP1A2 isoenzyme. With the combined use of Avelox with warfarin prothrombin time and other parameters of blood coagulation unaffected.

In patients treated with anticoagulants in combination with antibiotics, including with moxifloxacin, there are instances of increasing anticoagulant activity of anticoagulant drugs. Risk factors are the presence of an infectious disease (and the accompanying inflammatory process), age and general condition of the patient. Despite the fact that the interaction between moxifloxacin and warfarin is not detected, patients receiving combined treatment with these drugs, it is necessary to conduct monitoring of INR and adjust dose of oral anticoagulant drugs.

The interactions between moxifloxacin and oral contraceptives are not marked. There were no clinically significant interaction between glibenclamide and moxifloxacin. When combined therapy with moxifloxacin AUC itraconazole changed very slightly. In turn, itraconazole also has no significant effect on moxifloxacin pharmacokinetic parameters.

Therefore, the joint application of these drugs change the dosage for them is not required. Moxifloxacin and digoxin did not significantly affect the pharmacokinetic parameters of each other. When parenteral administration of morphine and simultaneous oral Avelox reduce bioavailability of moxifloxacin is not indicated; C max of moxifloxacin significantly reduced (17%).

Pharmacokinetics of atenolol significantly change under the influence of Avelox. After receiving a single dose of atenolol AUC increased by approximately 4%, while C max decreased by 10%. Probenecid does not affect the total clearance and renal clearance of moxifloxacin. With the combined use of moxifloxacin and probenecid dose correction is required. With the simultaneous use of activated charcoal and Avelox oral dose of 400 mg of systemic bioavailability is reduced by more than 80% as a result of slowing down its absorption. Pharmaceutical interaction of moxifloxacin infusion solution compatible with the following infusion solutions: sodium chloride 10% solution of sodium chloride 20% solution of sodium bicarbonate 4.2% solution of sodium bicarbonate 8.4%.

Terms and Conditions of storage

List B. The tablets should be stored out of reach of children, dry place at temperatures not above 25 ° C.

Shelf life - 5 years. List B. The solution for infusion should be stored in a dry, protected from light and away from children at a temperature of 8 ° to 25 ° C Do not freeze.

Shelf life - 5 years. After dilution with compatible solvents Avelox solution remains stable for 24 h at room temperature. Since the solution must not be frozen or cooled, it can not be stored in the refrigerator.

Upon cooling, the solution may Precipitatedisulphur, but at room temperature usually precipitate dissolves. The solution should be stored only in original container.

Deanol aceglumate

International name:
Deanola atseglumat (Deanol aceglumate)

Group Affiliation:
Noothropicals

Description of the active substance (INN):
Deanola atseglumat

Dosage form:
solution for oral

Mode of action:
Nootropic drug, on chemical structure similar to natural metabolites of the brain (GABA, glutamic acid). Has tserebroprotektornoe action, restores mental alertness, improves learning, easier processes for capturing, consolidating and play a memorable track. Stimulates tissue metabolism, increases the amplitude transkallozalnogo capacity, improve the organization of the basic rhythm of EEG and smooths the hemispheric asymmetry. Has a positive effect in neurotic states in elderly and senile, developed in the presence of organic insufficiency of the brain in alcohol-withdrawal syndrome.

Indications:
Astheno-depressive states (border states psychoorganic syndrome, schizophrenia, alcoholism), Neuroleptic malignant syndrome (correction of mild and severe forms); abstinent alcohol syndrome (with a predominance of asthenic disorders and somatovegetativnyh); intellectual mnestic violations, psychosomatic disorders, recovery period after transferred TBI, cerebrovascular disease (especially in elderly and senile).

Contraindications:
Hypersensitivity, infectious diseases, CNS, feverish condition, blood diseases, psychotic conditions, renal and / or hepatic impairment, epilepsy, pregnancy, lactation.

Side effects:
Allergic reactions, headaches, sleep disturbances, constipation, weight loss, itching in some cases - Depression (elderly people). Overdosage. Symptoms: increased side effects. Treatment: removal of preparation, method of activated carbon. If necessary - to be hospitalized.

Dosage and administration:
Inside, 1 g (1 ch.lozhka) 2-3 times daily, last admission - no later than 16-18 hours on average daily intake for adults - 4-6 g, for children - 0.5-2, the maximum single dose - 2 g, the maximum daily dose - 10 g, duration of treatment - 1.5-2.5 months, 2-3 times a year.

Cautions:
During the period of treatment must be careful when driving and other lesson potentially dangerous activities which require high concentration of attention and speed of psychomotor reactions.

Interaction:
Perhaps reinforcing the drugs that stimulate the central nervous system.


Description Demanol product is not intended for purposes of treatment without the participation of a physician.

DEANOL ACEGLUMATE

Pharmacological action

Nootropic drug, on chemical structure similar to natural metabolites of the brain (GABA, glutamic acid). Has tserebroprotektornoe action, restores mental alertness, improves learning, easier processes for capturing, consolidating and play a memorable track. Stimulates tissue metabolism, increases the amplitude transkallozalnogo capacity, improves the organization of EEG basic rhythm and smooths hemispheric asymmetry. Has a positive effect in neurotic states in elderly and senile, developed against the background of organic insufficiency of the brain in alcohol-abstinent syndrome.


Pharmacokinetics

C max in the CNS after oral administration is achieved by 0.5-1 h, to a lesser extent penetrate into the liver, lungs, heart, kidneys. T 1 / 2 to 24 h, displayed by the kidneys.


Statement

Astenodepressivnye state (border states psychoorganic syndrome, schizophrenia, alcoholism), Neuroleptic malignant syndrome (correction of mild and severe forms), abstinence alcohol syndrome (with a predominance of asthenic disorders and somatovegetativnyh), intellectual mnesticheskih violations, psychosomatic illness, during convalescence after suffered traumatic brain injury, cerebrovascular disease (especially in elderly and senile).


Dosage regimen

Inward 1 g 2-3 times / day, the last admission - no later than 16-18 hours on average daily intake for adults - 4-6 g, for children - 0.5-2, the treatment duration - 1.5-2.5 months, 2 - 3 times a year.

Maximum dose: single - 2 grams daily - 1910


Side effect

Perhaps: allergic reactions, headaches, sleep disturbance, constipation, weight loss, itching.

In some cases: depression (elderly patients).


Contraindications

Hypersensitivity, infectious diseases, CNS, feverish condition, blood diseases, psychotic conditions, renal and / or hepatic impairment, epilepsy, pregnancy, lactation.


Application of pregnancy and breastfeeding

Deanol atseglumat contraindicated during pregnancy and lactation (breastfeeding).


Cautions

Effects on ability to drive vehicles and management mechanisms

During the period of treatment should refrain from driving motor vehicles and classes of potentially hazardous activities that require high concentration and speed of psychomotor reactions.


Drug Interactions

Perhaps strengthening the action of drugs stimulating the central nervous system.

DE-NOL

Pharmacological properties: The antiulcer drug. Has Cytoprotective effect. In an acidic medium De-Nol formed on the surface of ulcers and erosions of the protective film, which contributes to their scarring and protects from the effects of gastric juice. De-Nol stimulates the synthesis of prostaglandin E 2, stimulates the secretion of mucus and bicarbonate ions, leads to the accumulation of epidermal growth factor in the area of the defect, reduces the activity of pepsin and pepsinogen. In addition, De-Nol has a bactericidal action against Helicobacter pylori - a microorganism that contributes to the development of chronic gastritis type B and peptic ulcers.

Bismuth subtsitrat practically not absorbed in the digestive tract, only a small amount of bismuth can enter the systemic circulation. Bismuth, enters the blood, excreted in the urine, and its concentration in blood plasma after treatment rapidly decreases. De-Nol is derived mainly from the feces.

INDICATIONS: Peptic ulcer and duodenal ulcer, gastritis, including those associated with Helicobacter pylori (H. pylori in the schemes of therapy), chronic gastritis and gastro exacerbation, including those associated with Helicobacter pylori; functional dyspepsia is not caused by organic diseases of the digestive tract erosive-ulcerative lesions of the mucous membrane of the stomach and duodenal ulcers caused by NSAID intake; syndrome irritable colon that occurs with diarrhea.

USE: Adults and children over the age of 12 years prescribed 1 tablet 4 times a day for 30 minutes before breakfast, lunch and dinner and the 4-th time before going to bed or 2 tablets 2 times a day for 30 minutes before eating. The tablet is drunk 1-2 sips of water (not milk).

Children aged 8-12 years, appoint 1 tablet 2 times a day for 30 minutes before meals, 4-8 years - with a dose of 8 mg / kg / day, the daily dose is divided into 2 admission. Accepted 30 minutes before eating.

Therapy is carried out within 4-6 weeks. If necessary, it can be extended to 8 weeks, then make a break for 8 weeks, during which it is not recommended to take other drugs containing bismuth.

If you find a patient persistence Helicobacter pylori is expedient to combine medication De Nolom 1 tablet 2 times daily in combination with oral clarithromycin 500 mg 2 times a day, with amoxicillin (Flemoxin solutab) 1 g 2 times a day for 7 days.

If necessary, appoint quadrotherapy: with De Nolom of 120 mg 2 times a day recommended to assign tetracycline 500 mg 4 times daily, metronidazole 500 mg 3 times daily in combination with a proton pump inhibitors (omeprazole, lansoprazol, rabeprazole or esomeprasol) in the standard therapeutic dose.

Duration of combination therapy - 7-14 days. To improve regeneration in ulcerative defect can be further treated De Nolom: 1 tablet 4 times a day for 30 minutes before breakfast, lunch and dinner, and 4 th time - before bedtime. The total duration of treatment De Nolom - up to 6 weeks (no more than 8 weeks).

Contraindications: severe renal dysfunction.

SIDE EFFECTS: possible nausea, vomiting, diarrhea, rarely - skin rash, itching.

Cautions: formed by the reception of De-Nol bismuth sulfide can be painted stool in black color. Such a change can be easily distinguished from the feces mixed with blood.

For 30 minutes before and after taking the drug should not eat milk and antacid drugs, because the presence of gastric juices necessary for the formation of a protective layer.

During pregnancy and breastfeeding is not recommended to use the drug.

INTERACTIONS: When the joint application of De-Nol reduces the absorption of tetracycline.

With simultaneous application of De-Nol with other medications containing bismuth, increasing the risk of increasing the concentration of bismuth in the blood.

OVERDOSE: If frequent the drug in high doses may develop symptoms of reversible dysfunction of the liver, raising the level of bismuth in blood serum. Therapy is symptomatic.

Storage conditions: at a temperature of 15-25 ° C.

Bismuthate tripotassium dicitrate

International name:
Bismuth tripotassium ditsitrat (Bismuthate tripotassium dicitrate)

Group Affiliation:
Intestinal antiseptic and astringent

Description of the active substance (INN):
Bismuth tripotassium ditsitrat

Dosage form:
tablets, tablets coated

Mode of action:
Antiulcer vehicle with bactericidal activity against Helicobacter pylori, also possesses anti-inflammatory and astringent properties. At pH 4 and below (gastric juice), the insoluble precipitate of bismuth oxychloride and citrate, chelate compounds are formed with the protein substrate (insoluble protective coating at the site of ulcer). By increasing the synthesis PgE, which increases mucus and bicarbonate secretion, stimulates the activity of cytoprotective mechanisms. Leads to accumulation of epidermal growth factor in the area of the defect. Reduces the activity of pepsin and pepsinogen. Improves the protective properties of the mucous membrane of the digestive tract. Increasing production of mucus, mucosal resistance to the effects of pepsin, HCl and enzymes.

Indications:
Peptic ulcer and 12 duodenal ulcer (in acute), chronic gastritis (including associated with Helicobacter pylori); dyspepsia not associated with organic gastrointestinal diseases.

Contraindications:
Hypersensitivity, chronic renal failure, pregnancy, lactation.

Side effects:
Nausea, vomiting, diarrhea, allergic reactions. With prolonged use at high doses - encephalopathy associated with the accumulation of Bi in TsNS.Peredozirovka. Symptoms: the development of renal dysfunction. Treatment: gastric lavage, the appointment of activated charcoal and saline laxatives drugs, symptomatic therapy, dialysis.

Dosage and administration:
Inside, adults - 120 mg 4 times a day (3 times for 30 minutes before eating and 2 hours after last meal) for children older than 12 years - 2 times a day to 240 mg on an empty stomach (30 minutes before eating), children under 12 years - 120 mg 2 times daily, with a small amount of water (not milk) within 28-56 days, after which it is necessary to make a break for 8 weeks. For the effect on Helicobacter pylori combined with oral metronidazole - 250 mg 4 times daily and amoxicillin 250 mg 4 times a day (with hypersensitivity to amoxicillin tetracycline use - 500 mg 3 times daily) for 10 days.

Cautions:
In the treatment of fecal staining is observed in the black.

Interaction:
For 30 minutes before and after the appointment should refrain from eating, antacid drugs and fluids. During the therapy should not eat ethanol. Reduces the absorption of tetracycline. Or combined with other Bi-containing drugs increases the risk of side effects (increase in Bi concentration in plasma). Antacids drugs with local action reduces the effect of bismuth tripotassium ditsitrata.


Description of the drug De-Nol is not intended for purposes of treatment without the participation of a physician.

Ciclopirox

International name:
Tsiklopiroks (Ciclopirox)

Group Affiliation:
Antifungal

Description of the active substance (INN):
Tsiklopiroks

Dosage form:
vaginal cream, cream for topical application, nail polish, vaginal suppositories

Mode of action:
Antifungal broad-spectrum drugs. Active against: Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton verrucosum, Trichophyton tonsurans, Trichophyton quinckeanum, Trichophyton equinum, Trichophyton concentricum, Trichophyton epilans, Trichophyton ferrugineum, Trichophyton gallnae, Trichophyton schoenleinii, Trichophyton soudanense, Trichophyton terrestre, Trichophyton violaceum, Microsporum canis, Microsporum gypseum, Microsporum audouini, Microsporum langeroni, Microsporum nanum, Epidermophyton floccosum, Candida (Candida albicans, Candida tropicalis, Candida krusei, Candida parapsilosis, Candida pseudotropicalis, Candida lipolytica, Candida quiliermondii, Candida brumpti, Candida utilis, Candida viswanathii), Cryptococcus neoformans, Histoplasma capsulatum, Sporotrichum schenckii, Torulopsis glabrata, Blastomyces dermatidis, Paracoccidioides braziliensis, Saccharomyces cerevisiae, Torula Bergeri, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Penicillium chrysogenum, Penicillium notatum, Absidia corymbifera, Mucor miehei, Paecilomyces varioti, Fusarium solani, Madurella grisea , Madurella mycetomi, Allescheria boydii, Cladosporium carrionii, Cladosporium trichoides, Philophora jeanselmei, Philophora pedrosoi, Philophora gougeroti, Hormodendrum dermatidis, Pyrenochaeta romeroi, Leptosphaeria senegalensis. It has antibacterial activity against Gram-positive and most Gram-negative pathogens. Suppresses the development of mycoplasmas and Trichomonas.

Indications:
Treatment and prevention of fungal infections of the skin and mucous membranes (including colored lichen, onychomycosis, fungal vaginitis, and vulvovaginitis).

Contraindications:
Hypersensitivity, pregnancy, lactation, children's age (10 years).

Side effects:
Local reactions (rare): itching, burning or skin irritation, hyperemia and peeling skin around the affected nail; allergic reactions.

Dosage and administration:
Outwardly, vaginally. The solution is for external use or cream: applied to the affected area and gently rubbing it 2 times a day. Treatment should be undertaken before the disappearance of skin effects (usually 2 weeks). In order to prevent recurrences is recommended to continue treatment for a further 1-2 weeks after symptoms disappear. The prevention of mycosis powder for external use (powder) is poured into socks or shoes. In the treatment and prevention of vaginitis and vulvovaginitis are using vaginal formulations - cream for intravaginal application, vaginal suppositories or solution (in the form of douching). The solution: to use douching 0.2% solution of Single bottle with a tip 1 times a day for 5 days. Vaginal cream: 1 time per day in the evening, before bedtime injected deep into the vagina with an applicator attached single-use (1 dose - 5 g) . For each procedure using a new single-use applicator. To prevent re-infection should be further processed neighboring skin vagina (external genitalia until the anus). To do this, squeezing from a tube a small amount of cream, apply it on the processed area with a cotton swab. Treatment duration - 6 days, if necessary, treatment is continued until 14 days. Vaginal Suppositories: 1 suppository (100 mg) once a day for 3-6 days, depending on the severity of the disease. Do not exclude the possibility of "ping-pong" effect. In order to prevent re-infection should be simultaneous treatment of sexual partners. Treatment of onychomycosis: length - from 4 to 28 weeks, depending on the severity of the case, the average length - about 12 weeks. The solution should be applied several times a day cream - in the evening. In order to improve treatment should be changed regularly skive all material and nails to apply a protective bandage from the film (in the evening rubbing in a large number of nail cream, give it a little dry and the bandage, the bandage is removed in the morning and several times during the day rubbing a nail solution preparation). Varnish is applied thinly to the affected nail is 1 time per day during the first month after the day of the second - 2 times a week, the third - one day a week. Duration of treatment should not exceed 6 months. 1 time per week varnish removed using a conventional solvent or after a warm bath scouring its upper layer.

Cautions:
Avoid contact with mud and cream in his eyes. It is recommended that simultaneous treatment of sexual partners. During the treatment is not recommended to use cosmetic nail polish. With long-term external use of the drug may be the phenomenon of sensitization.

Interaction:
The effect of increasing systemic antifungal drugs.

DAUNORUBICIN

Pharmacological action

Antitumor agents from the group of anthracycline antibiotics produced by Streptomyces coeruleorubidis. Cytotoxic effect due to the ability to inhibit the synthesis of DNA, RNA and proteins. The mechanism of action is based on the anthracycline intercalation between adjacent base pairs of the double helix of DNA, which prevents her "deploying" for further replication.


Pharmacokinetics

After i / v administration quickly distributed in the body, especially in the kidneys, spleen, liver, heart. Do not cross the BBB. Metabolised in the liver with the formation of the active metabolite daunorubitsinola.

T 1 / 2 in the initial phase of 45 min, in the final phase - to daunorubicin 18.5 h, for daunorubitsinola 26.7 h for the other metabolites of 55 hours is derived from the kidneys and bile.


Statement

Acute leukemia, lymphogranulomatosis, chorionepithelioma cancer, neuroblastoma, Ewing's tumor, Wilms' tumor, non-Hodgkin's lymphoma.


Dosage regimen

Set individually, depending on the testimony and stage of disease, the state of the hemopoietic system, the scheme of anticancer therapy.


Side effect

On the part of the hemopoietic system: anemia, leukopenia, thrombocytopenia.

On the part of the digestive system: nausea, vomiting, diarrhea, stomatitis.

Since the cardiovascular system: heart failure, arrhythmias, rarely - myocarditis, pericarditis.

On the part of the reproductive system: amenorrhea, azoospermia.

Other: alopecia, allergic reactions, headache.

Local reactions: pain at the injection site, tissue necrosis (for violation of technology introduction).


Contraindications

Leukopenia (leukocyte count below 4000/mkl), thrombocytopenia (platelet count below 120 000/mkl), chronic heart failure in the stage of decompensation, marked disturbances of liver function and / or kidneys, stomach ulcer and duodenal ulcer in acute, pregnancy, increased sensitivity to daunorubicin.


Application of pregnancy and breastfeeding

Daunorubicin is contraindicated in pregnancy. If necessary, use during lactation should stop breastfeeding.

Women of childbearing age should use reliable methods of contraception during therapy daunorubicin.

In experimental studies found teratogenic, embryotoxic effect of daunorubicin.


Cautions

With caution to patients with impaired renal function and / or liver, heart disease (including history), gout or nephrolithiasis (including history), as well as in patients treated with or receiving at present during combination chemotherapy other antitumor drugs, providing myelotoxic action or course of radiotherapy.

Do not recommend the use of Daunorubicin in patients with chickenpox (including recent recover or after contact with sick), with herpes zoster, or other acute infectious diseases.

Before and during treatment requires monitoring of peripheral blood picture, renal function, liver, chest radiography, ECG, echocardiography, determination of the stroke volume of the heart.

The frequency of cardiotoxic side effects increases if the total course dose daunorubicin than 400 mg / m 2 in adults and 300 mg / m 2 in children. Violations of the myocardium, the symptoms of chronic heart failure and other cardiotoxic effects of daunorubicin may occur several months or even years after treatment (especially in children), so control of the functional state of the cardiovascular system should be a long time.

Does not recommend vaccination of the patient or his family.

Do not recommend the use of daunorubicin in patients who previously received complete cumulative doses of doxorubicin. If the resulting course of the cumulative dose of doxorubicin below, the total dose of daunorubicin and doxorubicin should not exceed 550 mg / m 2.

In the first few days of daunorubicin may be painted in the urine red.


Drug Interactions

With the simultaneous use of medications that have myelotoxic action may strengthen the toxic effects.

In the application of cyclophosphamide or doxorubicin increases the risk of cardiotoxic effects.

When combined therapy with methotrexate (or other drugs with hepatotoxic effect) increases the probability of hepatotoxic effects.

Application of daunorubicin with urikozuricheskimi drugs increases the risk of nephropathy.

Daunorubicin liposomal

International name:
Liposomal Daunorubicin (Daunorubicin liposomal)

Group Affiliation:
Antitumor agents, antibiotic

Description of the active substance (INN):
Daunorubicin liposomal

Dosage form:
Concentrate for solution for infusion

Mode of action:
The antitumor antibiotic anthracyclines, produced by Streptomyces coeruleorubidis, with cytostatic effect. It acts on the S-phase of mitosis. Blocks matrix function of DNA, disrupting the synthesis of nucleic acids and protein. It is believed that the mechanism of action is based on the anthracycline intercalation between adjacent base pairs of the double helix of DNA, which prevents its deploying for subsequent replication. Antitumor activity is also realized through the interaction with membranes and the formation of free radicals of semiquinone type. Characterized by high antimitotic activity and high (in contrast to neliposomalnogo daunorubicin) selectivity of action. It is believed that the mechanism for delivery daunorubicin in solid tumors is associated with increased permeability of the vascular network of the tumor for some of the particles, similar in size to the vesicles liposomal daunorubicin. Inside the vesicles tumor drug penetrate into the tumor cell, after which the cleavage of liposomes with release into the cell-free daunorubicin. In addition, free daunorubicin in the measured concentrations present in plasma, which could further enhance the antitumor effect. The study of the therapeutic action showed a higher efficiency effects on solid tumors of liposomal daunorubicin in front of the ordinary.

Indications:
Kaposi's sarcoma against a background of HIV infection (in ineffectiveness of local therapy or systemic therapy with interferon alpha).

Contraindications:
Hypersensitivity (including to other anthracyclines or antratsendionam), severe depression of bone marrow function (leukopenia - the number of counts below 4 thousand / ml, granulocytopenia - less 750/mkl, thrombocytopenia - platelet count less than 120 thousand / ml) , decompensated chronic heart failure, end stage disease, cachexia, severe hepatic and / or renal failure, peptic ulcer and 12 duodenal ulcer (in acute), acute infectious diseases of viral, fungal or bacterial origin (including chicken pox, zoster). C care. The simultaneous use of lipid drugs for parenteral nutrition, depression of bone marrow hematopoiesis (including on a background of concomitant radiotherapy or chemotherapy, bone marrow infiltration by tumor cells), hyperuricemia (gout especially manifested or urate nefrourolitiazom), pregnancy, lactation, childhood and old age (safety and efficacy not established).

Side effects:
From the side of hematopoiesis: suppression of bone marrow hematopoiesis (anemia, leukopenia, granulocytopenia, thrombocytopenia). On the part of the SSA: increased blood pressure (nesimptomaticheskoe), syncope; potentially feasible (at high doses - more than 300 mg / sqm) development of CH (arrhythmia, tachycardia, shortness of breath, swelling of the ankles). On the part of the digestive system: dry mouth, tooth pain, dysphagia, nausea, vomiting, diarrhea, tenesmus, abdominal pain, ulceration of the mucous membrane of the gastrointestinal (ulcerative stomatitis and esophagitis, etc.) . the nervous system: headache, drowsiness or insomnia, tremor. On the part of the urinary system: dysuria, nocturia, or polyuria. On the part of the sense organs: eye pain, conjunctivitis, tinnitus. Allergic reactions: skin rash, itching; infusion reaction - back pain, a feeling of compression in the chest (there in the first 5-10 min infusion, and are at lower speeds infusion or its termination). Local reactions: at the injection site - phlebitis, painful inflammation (cellulitis), with exposure to skin - necrosis of surrounding tissues. Other: alopecia, hyperuricemia, opportunistic infections, lihoradka.Peredozirovka. Symptoms: mucositis, neutropenia, thrombocytopenia. Treatment: symptomatic, the appointment of colony stimulating factor (filgrastim).

Dosage and administration:
Only in / for at least 30-60 minutes, the recommended starting dose - 40 mg / m 1 time in 2 weeks. Dose picked individually to obtain a positive effect and continue throughout the life of effectiveness. Before the introduction of the solution is diluted with 5% dextrose to a concentration of 0.2-1 mg / ml. The finished solution should be used no later than 6 h after preparation. Patients with impaired renal function reduce the dose - when the concentration of serum creatinine above 0.3 mg / dL is recommended to use half the usual dose. If the liver function and concentration of bilirubin in the blood serum of 20.5 -51.3 mmol / l should use 3 / 4 normal doses at a concentration of bilirubin above 51.3 mmol / L - half the normal dose.

Cautions:
Treatment should be conducted in a specialized department specialist with experience in anti-tumor chemotherapy. Should be used only freshly prepared solution of the drug. Before and during treatment is necessary to monitor patterns of peripheral blood of renal function, liver, CAS (echocardiography, EKG). The treatment of anthracycline In most patients there may be alopecia, which is less pronounced in the treatment of liposomal daunorubicin and disappears after 5 weeks or more after completion of therapy. Particular attention should be paid to patients receiving combination chemotherapy with other anticancer drugs that have a dampening effect on bone marrow function . should exercise caution when using in conjunction with lipid preparations for parenteral nutrition, and together with other liposomal products. When in / introduction should take precautions to avoid extravasation of the drug, and avoid contact with eyes. It must be borne in mind that the use of the drug may cause heritable genetic changes. Male patients should be carefully observe measures of contraception during therapy and for 6 months after treatment. Women should avoid pregnancy during treatment. Application neliposomalnogo daunorubicin may lead to the Commission and the CHF. Such side effects have been observed in clinical use of liposomal daunorubicin. Nevertheless, it should consider the possibility of cardiotoxic actions, so all patients receiving the drug should be subjected to during the entire course of treatment is often the ECG examination. Transient ECG changes, such as flattening of the T wave, reduction of ST segment and clinically insignificant arrhythmias, are not indications to stop therapy. Reduction of QRS voltage is a more specific manifestation of the cardiotoxic actions. When this change should consider the possibility of conducting specific tests to most accurately detect myocardial damage induced by anthracyclines, - a biopsy of the endocardium. Compared with the ECG a more specific method for the evaluation and monitoring of cardiac function is the measurement of left ventricular ejection fraction. These methods should be used in patients with increased risk for the Commission before the start of therapy (including those with a history of disease CAS) and periodically during treatment, especially in cases where the cumulative dose exceeds 800 mg / sqm. If signs of CMS (the decline of left ventricular ejection fraction compared with that before the start of therapy and / or value of the indicator of clinically meaningful reduced - less than 45%) should be endocardial biopsy. It is necessary to carefully assess the ratio of potential benefits from further therapy and the risk of irreversible damage to the heart muscle. CHF as a result of the Commission may develop suddenly, without previously observed changes in ECG, and can occur several weeks after cessation of therapy. When calculating the total dose should be considered as dose cardiotoxicity of drugs (including other anthracyclines, antratsendionov, 5-fluorouracil and etc.) derived or received by the patient. During the period of treatment is not recommended immunization with viral vaccines, should also avoid contact with bacterial infections and contact sports classes, which are likely to hemorrhage and trauma (especially in patients with depression of bone marrow hemopoiesis).

Interaction:
Side effects in the interaction with antiretroviral drugs were observed. Pharmaceutical incompatible with heparin and dexamethasone phosphate (daunorubicin precipitate formed), highly alkaline solutions (pH over 8, because of the instability of the glycosidic linkage daunorubicin), 0.9% solution of NaCl (aggregation of liposomes), impurities contained bacteriostatic agents - benzyl alcohol or other substance detergentopodobnye (can cause rupture of the membrane bilayer of liposomes, leading to a premature leak of the active ingredient). The solvent can be used only 5% dextrose. Compatible with vincristine, cyclophosphamide, 6-mercaptopurine, prednisolone, L -asparaginase, methotrexate. Hepatotoxic drugs (including methotrexate) increase the risk of liver problems. Ap. anticancer drugs enhance the therapeutic effect and severity of bone marrow suppression. cyclophosphamide, radiation therapy, other anticancer drugs, medications Li + increase the cardiotoxicity. arthrifuge reduces the effect of allopurinol, colchicine, sulfinpirazon blockers and tubular secretion (may require adjustment of doses of drugs arthrifuge; to eliminate hyperuricemia, arising during the treatment of liposomal daunorubicin, allopurinol is preferred because urikozuricheskie arthrifuge drugs increase the risk of nephropathy). With the introduction of live virus vaccines available vaccine virus replication and increased adverse effects of inactivated vaccines - decrease production of antiviral antibodies.