Composition, structure and packing

Syrup: Clear, dark brown color, sweet flavor and aroma. 100 g of liquid extract of plantain 3 g liquid extract of thyme in 1915 Excipients: Methyl-4-hydroxybenzoate, propyl-4-hydroxybenzoate, invert sugar solution (dextrose, fructose, sucrose), purified water.

Clinico-pharmacological group: Phitopreparation with expectorant and anti-inflammatory action.

Pharmacological action

Phitopreparation with expectorant and anti-inflammatory action.


In the complex therapy of inflammatory diseases of the respiratory tract, accompanied by a cough with phlegm trudnootdelyaemoy, as well as spastic cough:

Dosage regimen

The syrup should be taken undiluted after a meal. Duration of drug administration is determined individually, depending on the severity of the disease, the mild form is 2 weeks. We recommend taking the drug as early as 2-3 days after the disappearance of symptoms. The patient must notify the need to consult a doctor, if after 2-3 weeks improvement was not observed.

Side effect

Possible: allergic reactions (including the content contained in the product alkyl-4-hydroxybenzoate). The patient must notify the need to consult a doctor with the appearance of side effects.

Hypersensitivity to the drug's components.

With caution (due to the presence of ethanol) will appoint a drug to treat liver diseases, chronic alcoholism, epilepsy, brain trauma, as well as children.

With careful use the drug in patients with diabetes and in patients who are on a diet low in carbohydrates.

Pregnancy and lactation

With caution (because of the presence of ethanol) will appoint a drug during pregnancy, during breast-feeding.

Application for violations of liver function

With caution (because of the presence of ethanol) will appoint a drug to treat liver diseases.


In the appointment of the drug should be aware that syrup contains 6.5 vol.% Ethanol. The total sugar content (in terms of sucrose) is 0.6 g / ml. In 1 teaspoon (5 ml) contains 0.25 XU or 3.0 g of sucrose in 1 tablespoon (10 ml) - 0.5 XE or 6.0 g of sucrose. We do not recommend the simultaneous use of antitussive drugs. When opacification syrup or precipitate the drug should not be used.


Data on drug overdose is not granted.

Drug Interactions

Because the content of ethanol a drug enhances action sedatives, hypnotics and other central depressant drug.

Terms and Conditions of storage

The drug should be stored at temperatures not above 25 ° C in the reach of children. Shelf life - 3 years.


Composition, structure and packing

Capsules are white or yellowish-white; content capsules - powder white or yellowish. 1 capsule. tseftibuten 400 mg. Excipients: microcrystalline cellulose, sodium starch glycolate, magnesium stearate. The composition of the capsule shell: titanium dioxide.

Powder for Oral suspension from light yellow to dark yellow, the water forms a light-yellow suspension with a characteristic cherry scent. 1 ml final suspensions. tseftibuten (in the form of dihydrate) 36 mg. Excipients: Xanthan gum, sucrose, Simethicone, silicon dioxide, polysorbate 80, sodium benzoate, food additives with cherry taste.

Clinico-pharmacological group: cephalosporins III generation.

Pharmacological action

Cephalosporins III generation. Is beta-lactam antibiotic has a bactericidal effect, the mechanism of which is due to suppression of synthesis of the bacterial cell wall. Features of the chemical structure tseftibutena determine its high resistance to β-lactamases, which accounts for activity against many microorganisms producing β-lactamases and resistant to penicillin and other cephalosporins. Tseftibuten vysokoustoychiv to penicillinase plasmid and tsefalosporinazam, but is sensitive to the action of certain chromosomal tsefalosporinaz which are produced Citrobacter spp., Enterobacter spp. and Bacteroides spp. The drug should not be used for infections caused by strains of bacteria, whose stability to beta-lactam antibiotics due to common mechanisms, such as changes of permeability or penicillin-binding proteins (PRP) (eg, penitsillinorezistentny Streptococcus pneumoniae). Tseftibuten interacts mainly with the PRP-3 Escherichia coli, which leads to the formation of filar forms at a concentration equal to 1/4-1/2 the IPC, and lysis at a concentration twice the IPC. The minimum bactericidal concentration tseftibutena for strains Escherichia coli, sensitive and resistant to ampicillin, approximately equal to the IPC. Active in vitro and in clinical practice for most strains of the following Gram-positive microorganisms: Streptococcus pyogenes, Streptococcus pneumoniae (excluding penitsillinorezistentnyh strains), Gram-negative microorganisms: Haemophilus influenzae (strains producing and not producing β-lactamases), Haemophilus parainfluenzae (strains producing and do not produce β-lactamase), Moraxella (Branhamella) catarrhalis (most strains produce β-lactamase), Escherichia coli, Klebsiella spp. (Including Klebsiella pneumoniae and oxytoca), indole-positive Proteus spp. (Including Proteus vulgaris), and Providencia spp., Proteus mirabilis, Enterobacter spp. (Including Enterobacter cloacae and Enterobacter aerogenes), Salmonella spp., Shigella spp. Active in vitro against most strains of these organisms, but its clinical efficacy has not been established; gram-positive organisms: Streptococcus spp. Groups C and G; Gram-negative microorganisms: Brucella spp., Neisserria spp., Aeromonas hydrophilia, Yersinia enterocolitica, Providencia rettgeri, Providencia stuartii strains and Citrobacter spp., Morganella spp. and Serratia spp., which do not produce large quantities of chromosomal tsefalosporinazy. Inactive against Staphylococcus spp., Enterococcus spp., Acinetobacter spp., Listeria spp., Flavobacterium spp. and Pseudomonas spp., weakly active against most anaerobes, including most strains of Bacteroides. Tseftibuten-trans does not have microbiological activity in vitro and in vivo against the same strains.



After taking the drug inside tseftibuten almost completely absorbed from the gastrointestinal tract (90%). Cmax was reached after 3 h after a single oral capsules 400 mg. Bioavailability tseftibutena depends on the dose in the therapeutic dose range (≤ 400 mg). The speed and extent of absorption tseftibutena when receiving Tsedeksa in the form of suspension changes, while taking a high-calorie fatty foods.


Cvyazyvanie tseftibutena to plasma proteins is low (62-64%). There are no adequate data on the concentration in the cerebrospinal fluid tseftibutena not, but when taking other cephalosporins into their content in the cerebrospinal fluid usually does not reach therapeutic levels. After receiving a single oral dose of tseftibutena 200 mg it was not detected in breast milk in lactating women. In young adult volunteers Css tseftibutena (when given every 12 h) in plasma were achieved after receiving the fifth dose. A notable cumulation of the drug with repeated use is not marked. Studies have shown that tseftibuten easily penetrates into a liquid medium and tissues. In a liquid skin bubble concentration tseftibutena was comparable to that in plasma or exceeded it (on the basis of comparison AUC). Tseftibuten penetrated into the middle ear fluid in children with acute otitis media, where its concentration was approximately equal levels in plasma or exceed it. Concentrations tseftibutena in lung tissue were approximately 40% of the concentrations in plasma. In nasal, tracheal and bronchial secretion, broncho-alveolar lavage fluid and cell suspension concentration tseftibutena were respectively about 46, 20, 24, 6 and 81% of the concentrations in plasma.

Metabolism and excretion

The main derivative tseftibutena circulating in plasma (tseftibuten-trans), apparently formed by direct conversion tseftibutena (cis-form). Concentration tseftibutena-trans in plasma or urine is usually around 10% or less of the concentration tseftibutena. T1 / 2 tseftibutena from the plasma of 2 to 4 hours (average 2.5 hours) and does not depend on the dose or use schemes. Write mainly unchanged in the urine. Tseftibuten detected in the urine within 24 h after administration of 400 mg; Cmax in urine was 264 ug / ml and was achieved during the first 4 h after 20-24 h after a single dose of the drug concentration in urine tseftibutena was 10.5 micrograms / ml.

Pharmacokinetics in special clinical situations

In elderly volunteers Css tseftibutena (when given every 12 h) were achieved after receiving the fifth dose. The average AUC in this group was slightly higher than in young adults. With repeated use tseftibutena in elderly accumulation was negligible. Pharmacokinetics tseftibutena not significantly changed with chronic active hepatitis, cirrhosis, alcoholic disease and other liver diseases, accompanied by necrosis of hepatocytes. AUC and T1 / 2 tseftibutena from plasma increased as renal failure.

In patients with creatinine clearance <5 ml / min, AUC and T1 / 2 were 7-8 times higher than in healthy individuals. A single hemodialysis leads to the elimination of approximately 65% of the dose tseftibutena from the plasma.


Treatment of infectious-inflammatory diseases caused by susceptible microorganisms:
infections of the upper respiratory tract (including pharyngitis, tonsillitis and scarlet fever in adults and children, acute sinusitis in adults, otitis media in children);
Infection of lower respiratory tract in adults (including acute bronchitis, exacerbation of chronic bronchitis and severe pneumonia) in those cases where the possible admission of drug inside, ie with community-acquired infections;
urinary tract infections in adults and children (including complicated and uncomplicated);
enteritis and gastroenteritis in children caused Salmonella spp., Shigella spp. and Escherichia coli (tseftibuten not active against Campylobacter spp. and Yersinia spp.).

Dosage regimen

Duration of therapy (as well as the use of other antibiotics for oral administration) is from 5 to 10 days.
In the treatment of infections caused by Streptococcus pyogenes, Tsedeks in a therapeutic dose should be applied for at least 10 days. For adults the recommended dose Tsedeksa is 400 mg / day. Tsedeks capsules can be taken irrespective of food.
In acute bacterial sinusitis, acute bronchitis, aggravation of chronic bronchitis and complicated and uncomplicated urinary tract infection drug may be used in a dose of 400 mg 1 time / day.
In community-acquired pneumonia and the possibility of taking the drug inside the recommended dose Tsedeksa is 200 mg every 12 hours

Adult patients in violation of renal function change in dose is required only for reducing the spacecraft is less than 50 ml / min. When spacecraft from 49 to 30 ml / min daily dose should be reduced to 200 mg or designate by 400 mg every 48 hours (a day), with the spacecraft from 29 to 5 ml / min recommended daily dose is 100 mg or a drug prescribed for 400 mg every 96 hours (3 days). In patients receiving hemodialysis for 2 or 3 times a week, Tsedeks can be assigned to 400 mg at the end of each hemodialysis.

Children of drug is preferable to designate in the form of suspension, the recommended dose of 9 mg / kg / day. The maximum dose - 400 mg / day. Pharyngitis (including those with tonsillitis), acute purulent otitis media and urinary tract infections (including complications), the medication can be used 1 time per day. In acute bacterial enteritis in children daily dose can be divided into 2 divided doses (based on 4.5 mg / kg every 12 hours).

For children weighing over 45 kg or over the age of 10 years, the drug can be given at the recommended adult dose. Safety and efficacy Tsedeksa in children under 6 months are not installed. The suspension Tsedeksa can take approximately 1-2 hours before or after a meal. Before taking the drug vial must shake vigorously.

Side effect

Adverse events were recorded in patients who received Tsedeks:
On the part of the digestive system: nausea (≤ 3%), diarrhea (3%), rarely - indigestion, gastritis, vomiting, abdominal pain, increased activity of AST, ALT and LDH, very rarely - the growth of Clostridium difficile, combined with moderate or marked diarrhea.
From the side of the central nervous system: headache, rarely - dizziness, rarely recorded seizures, which were not definitely related to treatment (convulsions were observed 5 days after starting treatment Tsedeksom one elderly patient with chronic obstructive lung disease who had received various drugs, including theophylline ).
On the part of the hemopoietic system: reduction of hemoglobin, leukopenia, eosinophilia, thrombocytosis. Adverse events were recorded in patients in the treatment of various cephalosporins Allergic reactions: anaphylaxis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis.
On the part of the digestive system: marked diarrhea, colitis, increased levels of bilirubin.
On the part of the hemopoietic system: aplastic anemia, hemolytic anemia, bleeding, positive direct Coombs test, pancytopenia, neutropenia and agranulocytosis.
From the urinary system: kidney, toxic nephropathy, Glycosuria, ketonuria. Other: superinfection.

In clinical studies in approximately 3000 patients demonstrated the safety and tolerability of good Tsedeksa. Most adverse events were mild and transient marked and rare or very rare. Most adverse reactions yielded symptomatic therapy or were after the abolition Tsedeksa.

Hypersensitivity to any component drug and to other cephalosporins.

Pregnancy and lactation

Adequate and strictly controlled studies safety and efficacy of the drug during pregnancy and childbirth were not conducted. The results of studies of the effect of drugs on reproductive function in animals is not always possible to predict their effects in humans, so if the decision to appoint Tsedeksa during pregnancy should assess the intended benefits to the mother and the potential risk to the fetus. Tseftibuten not excreted in breast milk.

Application for violations of renal function

Adult patients in violation of renal function change in dose is required only for reducing the spacecraft is less than 50 ml / min. When spacecraft from 49 to 30 ml / min daily dose should be reduced to 200 mg or designate by 400 mg every 48 hours (a day), with the spacecraft from 29 to 5 ml / min recommended daily dose is 100 mg or a drug prescribed for 400 mg every 96 hours (3 days).

Patients receiving hemodialysis 2 or 3 times a week, Tsedeks can be assigned to 400 mg at the end of each hemodialysis.


Precautions should be appointed Tsedeks patients with complicated gastrointestinal diseases in history (especially in chronic colitis). Extremely cautiously prescribe cephalosporin to patients with known or suspected allergic to penicillin. Approximately 5% of patients with allergy to penicillin observed cross-reactivity to cephalosporins.

In patients treated with both penicillins and cephalosporins, are registered serious acute hypersensitivity reactions (anaphylaxis) have been known to cross with the development of hyperreactivity anaphylaxis.
In the event of serious anaphylactic reactions shown emergency treatment (eg, epinephrine, in / in the introduction of fluid, providing airway, the introduction of oxygen, antihistamines, corticosteroids, pressor amines, active surveillance).
In the treatment of broad spectrum antibiotics (including Tsedeksom) violation of the intestinal microflora can cause diarrhea, including pseudomembranous colitis associated with the elaboration of toxin Clostridium difficile.

Severity of diarrhea, accompanied or not by dehydration, can vary from mild to severe or life-threatening. Diarrhea may occur during or after antibiotic treatment. This diagnosis should be discussed in all the cases where persistent diarrhea appears on a background of reception of any broad-spectrum antibiotic such as Tsedeksa. Influences Tsedeksa the results of chemical or laboratory tests were found.
When using other cephalosporins sometimes recorded false-positive direct Coombs test. However, the results of studies using red blood cells of healthy people have not confirmed the ability Tsedeksa cause positive Coombs' test in vitro even at concentrations up to 40 mg / ml.


In case of accidental overdose Tsedeksa signs of toxicity were not observed. In healthy adult volunteers who received Tsedeks once at a dose of 2 g, serious adverse reactions were not, and all clinical and laboratory parameters were within normal limits. Treatment: specific antidote tseftibutena not exist, so an overdose can be gastric lavage. Much of the dose Tsedeksa can be removed from the blood by hemodialysis. The effectiveness of peritoneal dialysis is not installed.

Drug Interactions

In special studies investigated the interaction Tsedeksa with the following medications: antacids with aluminum hydroxide and magnesium in high doses, ranitidine, and theophylline (single in / in the introduction). No evidence of clinically significant interactions were found.

Influence Tsedeksa on plasma levels or pharmacokinetics of theophylline ingestion is not known. Information about the interaction with other drugs have so far been received.

Terms and Conditions of storage

The drug should be stored at 2 ° to 25 ° C. Prepared suspension can be stored for 14 days in the refrigerator (2 ° to 8 ° C). Shelf life of the drug in capsule form - 2 years, in the form of powder for suspension - 2.5 years.


Composition, structure and packing

Suspension for V / m introducing children homogenous, white; on standing formed a colorless supernatant and slowly precipitate of white color, breaks very easily with shaking. 0.5 ml of inactivated hepatitis A virus (strain HM 175) 720 ed.IFA. Excipients: aluminum hydroxide, 0.5 mg (sorbent), 2-Phenoxyethanol 5 mg (preservative), neomycin sulfate (traces), amino acids (mixture), formaldehyde, sodium hydrophosphate, potassium dihydrogen, polysorbate 20, potassium chloride, sodium chloride, neomycin sulfate (traces), water d / and.

The product contains formaldehyde inactivated hepatitis A virus (strain HM 175 hepatitis A virus) grown in human diploid cell MRC5, concentrated, and adsorbed on aluminum hydroxide. Suspension for i / m administration for adults homogenous, white; on standing formed a colorless supernatant and slowly precipitate of white color, breaks very easily when shaken. 1 ml of inactivated hepatitis A virus (strain HM 175) 1440 ed.IFA. Excipients: aluminum hydroxide, 0.5 mg (sorbent), 2-Phenoxyethanol 5 mg (preservative), amino acids (mixture), formaldehyde, sodium hydrophosphate, potassium dihydrogen, polysorbate 20, potassium chloride, sodium chloride, neomycin sulfate (traces), water q / and.

The product contains formaldehyde inactivated hepatitis A virus (strain HM 175 hepatitis A virus) grown in human diploid cell MRC5, concentrated and adsorbed on aluminum hydroxide.

Pharmacological action

A vaccine to prevent hepatitis A. It provides protection against hepatitis A, forming a specific immunity by inducing production of antibodies against hepatitis A virus (HAV), as well as activation of cellular mechanisms of immunity. Clinical studies have shown that 99% of vaccinated 30 days after the first dose is achieved seroprotektsiya (> 20 mIU / ml). The data obtained from two injections of vaccine with an interval of 6-12 months, allow us to conclude that 97% of vaccinated within 25 years after the course will have a protective antibody titer (> 20 mIU / ml). In studying the kinetics of the immune response it was found that after a single dose of vaccine Havriks in 79% of vaccinated seroprotektsiya attained on the 13th day, at 86.3% - to 15-day, at 95.2% - to 17-day, and in 99 % - to 19-day, ie these intervals are shorter than the average incubation period for hepatitis A (4 weeks). The effectiveness of the vaccine Havriks was estimated during outbreaks of diseases affecting large populations (Alaska, Slovakia, United States, Britain, Israel, Italy), as well as in the home, organized groups of children. These studies have shown that vaccination Havriks led to the cessation of outbreaks.

If coverage is not less than 80% susceptible contingent cropping outbreak reached within 4-8 weeks. In order to ensure long-term protection should be introduced a second (booster) dose between 6 and 12 months after the first dose.

It was found that revaccination, conducted in the period up to 12-60 months after vaccination, which induce the same level of antibodies, as well as revaccination, conducted in 6-12 months after vaccination. Based on the available data we can conclude that individuals with intact immune status after the course of vaccination, consisting of two doses, there is no need to conduct additional booster.


Data on the pharmacokinetics Havriks not available.

prevention of hepatitis A with 12 months of age.

Dosage regimen

Havriks not be entered into / in! The vaccine is designed to Havriks i / m injection.

Adults and children older vaccine should be injected into the deltoid region, and children 12-24 months - in the anterolateral thigh region. The vaccine should not be injected in the buttock, as well as s / c, since for such routes of administration of antibodies to hepatitis A virus may not reach the optimum level. Before the introduction of the vaccine should be explored visually to identify foreign particles and changes in appearance.

Immediately prior to the introduction of the vaccine vial or syringe should be shaken vigorously to obtain a slightly turbid white suspension. If the vaccine there is any deviation from the norm, then this package with the vaccine should be destroyed.

Vaccination schedules

A single dose primary vaccination for adults and adolescents over the age of 16 years is 1.0 ml for children and adolescents under the age of 16 years - 0.5 ml. Re-vaccination is carried out 6-12 months after vaccination, using a dosage appropriate to age. The optimal interval between vaccination is 6-12 months. Booster (booster), the effect achieved by the introduction of booster doses and in the period 12-60 months after the introduction of vaccinating dose.

Side effect

The vaccine is usually well tolerated. Local reactions: short-term pain at the injection site (assessed as severe in less than 0.5% of cases), redness and swelling (frequency - about 4% of the total number of vaccinations). General reactions: headache, malaise, vomiting, fever, nausea and loss of appetite (frequency - from 0.8% to 12.8% of total vaccinations). All of these adverse events were no effects were predominantly mild, with the duration of most of them did not exceed 24 hours

The nature of adverse reactions and symptoms in children was the same as in adults, but they have adverse reactions were observed less frequently. During the post-approval observations in rare cases, there were fatigue, diarrhea, myalgia, arthralgia, allergic reactions (including anaphylactoid reactions), as well as seizures.

Hypersensitivity to any vaccine component;
the presence of hypersensitivity reactions to previous vaccine Havriks.

Acute infectious and noninfectious diseases, exacerbation of chronic diseases are temporary contraindications for vaccination, with mild viral respiratory infections, intestinal disease vaccinations carried out immediately after the normalization of temperature.

Pregnancy and lactation

In the absence of adequate data in the application of the vaccine during pregnancy and during lactation are not recommended, despite the minimal risk of exposure to inactivated vaccine on the fetus and child. Havriks during pregnancy and lactation should be used only if there is absolute evidence.


Havriks not provide protection against hepatitis caused by other pathogens such as hepatitis B virus, hepatitis C virus, hepatitis E, as well as other known pathogens affecting the liver. Havriks should be administered with caution to patients with thrombocytopenia or with disorders of the blood coagulation system, because after i / m injections in such patients can cause bleeding. After the injection of such patients should apply a pressure bandage (not rubbing) not less than 2 minutes.

Patients with thrombocytopenia or disorders of blood coagulation system allowed n / a vaccine Havriks. Patients who are on hemodialysis, and patients with disorders of the immune system after a single dose of vaccine Havriks can not achieve an adequate development of antibody titer against hepatitis A. Such patients may require the introduction of additional doses of vaccine. As with the parenteral administration of any vaccine in the vaccination room should be all that is necessary for coping with a possible anaphylactic reaction to the vaccine Havriks. Vaccinated should be under medical observation for 30 minutes after immunization.

In regions with low or moderate endemichnostyu hepatitis A vaccination Havriks particularly recommended for those at risk of infection, as well as persons who have hepatitis A may have a severe course, or those whose disease is hepatitis A because of their professional affiliation can lead to outbreaks.

These include: persons traveling to hyperendemic regions or in regions where the flare recorded incidence of hepatitis A, members of military units deployed in areas with poor sanitary conditions or insecure water supply, persons with hepatitis A disease which, because of their professional affiliation can lead to outbreaks and for which there is a professional risk of acquiring hepatitis A virus (employees of schools and kindergartens, middle and junior medical staff, particularly in infectious, gastroenterological and pediatric hospitals, employees of sewerage and water treatment plants, the workers of public catering, food industry, grocery stores, the staff closed institutions of MDPA, social welfare and health facilities), persons residing or located in areas of hepatitis A (including family or living in areas where the recorded incidence of flare), persons with behavioral risk of acquiring hepatitis A virus (homosexuals, persons conducting sexually promiscuous, drug addicts who inject drugs), patients suffering from hemophilia, persons with household contact with infected (virus excretion may occur over a relatively long time in connection with the conduct of Vaccination is recommended for all persons in contact with an infected person), populations with known high incidence of hepatitis A, or those groups in which the incidence of hepatitis A increased due to low hygienic conditions), those with chronic liver disease or increased risk liver disease (chronic carriers of hepatitis viruses B, C, delta, persons with chronic hepatitis of alcoholic, autoimmune, toxic, pharmaceutical and other origin, persons with Wilson's disease, hepatosis and hepatopathy). In regions of moderate or high endemicity for hepatitis A vaccination is recommended for all susceptible populations.

Introduction Havriks vaccine against the passing of hepatitis A in the incubation period does not worsen the disease. Havriks can enter HIV-infected patients. The presence of antibodies to hepatitis A virus after the first vaccination is not a contraindication to revaccination.

Effects on ability to drive vehicles and management mechanisms



So far, cases of overdose vaccine Havriks not reported.

Drug Interactions

Havriks vaccine may be introduced simultaneously with inactivated vaccines, the National calendar of vaccination RF and immunization schedule an epidemic of Russia. Because the vaccine is an inactivated Havriks, it is unlikely that its simultaneous introduction with other inactivated vaccines will lead to a breach of the immune response.

With simultaneous injection of inactivated vaccines against typhoid, cholera, tetanus and yellow fever, reduce the immune response to the vaccine Havriks was not found. With simultaneous injection with immunoglobulins rights protective effect of vaccine is not reduced. If there is a need to introduce Havriks with other vaccines or immunoglobulins, the drugs are introduced with different syringes and needles in different parts of the body.

Terms and Conditions of storage

The vaccine should be stored and transported at a temperature of 2 ° to 8 ° C; not freeze. Shelf life - 3 years. Do not use after the expiry date stated on the package.


Composition, structure and packing

Solution for i / m injections transparent, ranging from colorless to yellow, viscous.

1 ml.fulvestrant 50 mg.

1 syringe (5 ml) fulvestrant 250 mg.

Excipients: ethanol 96% (100 mg / ml), benzyl alcohol (100 mg / ml), benzyl benzoate (150 mg / ml), castor oil (5 ml).

Clinico-pharmacological group: antiestrogens drug with antitumor activity.

Pharmacological action

The antitumor drug, antiestrogen. Fulvestrant is a competitive antagonist of estrogen receptors. The level of affinity to the receptors is comparable with estradiolom.Fulvestrant blocks trophic effect of estrogens, without showing their own estrogenopodobnoy activity. The mechanism of action is associated with suppression of the activity and degradation of estrogen receptors.

Also fulvestrant significantly decreased expression of progesterone receptors.

Fulvestrant does not have a stimulating effect on the endometrium in postmenopausal women. Effects of prolonged therapy on endothelium fulvestrant in postmenopausal women is not installed. Also, there are no data on the morphology of the endometrium.

Data on the impact of prolonged use of fulvestrant on bone tissue is not available.


Absorption and distribution

After i / m injection of fulvestrant is slowly absorbed, reaching a Cmax in the plasma after about 7 days. Absorption takes longer than 1 month, so if monthly injections are about 2-fold accumulation of the drug. Css in plasma determined approximately after 6 monthly injections, while the bulk of accumulation is reached after 3-4 injections.

After i / m injection exposure is approximately proportional to the dose introduced (in the range of doses from 50 to 250 mg).

In the equilibrium state the content of fulvestrant in the plasma varies in a relatively narrow range - maximum and minimum rates differ by about 2-3 times.

Fulvestrant is characterized by extensive and rapid distribution. Large apparent Vd (from 3 to 5 l / kg) in the equilibrium state involves mainly ekstravaskulyarnoe distribution.

Plasma protein binding is 99%. The main components include binding fractions VLDL, LDL and HDL. The role of sex hormone binding of globulin is not installed.


Metabolism of fulvestrant includes a combination of multiple potential pathways of biotransformation, similar mechanisms of metabolism of endogenous steroids (including metabolites of 17-ketone, sulfone, 3-sulfate, 3 - and 17-glucuronide).

Identified metabolites are less active or equal to the activity of fulvestrant. CYP3A4 isoenzyme is the only one who participates in the oxidation of fulvestrant. However, it appears that predominates in vivo biotransformation without the involvement of P450 isozymes.


T1 / 2 is 50 days.

Fulvestrant is mainly excreted in the feces, urine output less than 1% of the active substance.

Pharmacokinetics in special clinical situations

The pharmacokinetic profile of fulvestrant does not depend on age (range 33-89 years), weight (40-127 kg), and race.

Light and mild renal dysfunction do not have a clinically significant effect on the pharmacokinetics of fulvestrant.

Fulvestrant pharmacokinetics studies in patients with impaired liver function was carried out.

locally advanced or disseminated breast cancer with positive estrogen receptors in postmenopausal women with progression after or during therapy with antiestrogens.

Dosage regimen

The drug is introduced into / m, by slow injection.

For adult women (including elderly) the recommended dose is 250 mg 1 time per month.

In the case of light to moderate renal dysfunction (CC ≥ 30 ml / min) dose adjustment is required. Safety and efficacy in patients with severe impaired renal function (CC <30 ml / min) is not installed.

Precautions recommended Fazlodeks patients with mild or moderate hepatic impairment. Safety and efficacy in patients with impaired liver function is not installed.

Terms of use and handling of drug

Remove glass syringe body contour of the blister and make sure no damage.

Breaking the outer package of safe needles (SafetyGlide). Remove the needle case strictly according to its direction, so as not to damage the needle tip. Touch the needle during its use impossible.

Break jumper white plastic cover the tip of a syringe and remove the cover from the attached rubber plug tip. Rotational motion to consolidate the needle at the tip of the syringe. Remove the cover from the needle.

Visually estimate the state of solution for parenteral administration for the lack of particles and discoloration prior to use.

Remove excess gas bubbles from the syringe (small bubbles may remain). Slowly introduce the solution into the gluteal muscle.

After removing the needle from the gluteal muscles to immediately activate the needle safety device by pushing the lever to transfer to a forward position for as long as the needle tip is fully closed. For the convenience of the plane bevel needle tip location meets the lever on the device security. When you activate the protective mechanism may be minimal splashing liquids, which may remain on the needle after injection. Visually verify that the lever moved to the extreme position and the needle tip is fully closed. If you can not activate the protective device needle, immediately put the needle in a standard container for needles.

For maximum security, you should perform all manipulations with one hand away from yourself and others.

Side effect

Determining the frequency of adverse reactions: very common (> 10%), frequent (> 1 - ≤ 10%), rarely (> 0.1-≤ 1%).

On the part of the digestive system: frequent - nausea, vomiting, diarrhea, anorexia.

Since the cardiovascular system: very frequently - feel the heat ("hot flushes"); often - thromboembolism. Local reactions: often - transient pain and inflammatory reactions.

On the part of the urogenital system: often - urinary tract infections, rarely - vaginal bleeding, vaginal candidiasis.

Dermatological reactions: often - a rash. Allergic reactions: seldom - edema, urticaria.

Other: often - headaches, asthenia, back pain, rarely - galactorrhea.

marked disturbances of liver function;
Hypersensitivity to the drug's components.

Precautions appoint a drug in violation of the kidneys and liver.

Pregnancy and lactation

The drug is contraindicated during pregnancy and lactation.

Application for violations of liver function

Precautions appoint a drug in mild and moderately expressed violations of liver function.

Contraindications disturbancies liver function.

Application for violations of renal function

In the case of light to moderate renal dysfunction (CC ≥ 30 ml / min) dose adjustment is required. Safety and efficacy in patients with severe impaired renal function (CC <30 ml / min) is not installed.

We recommend caution when using Fazlodeksa in patients with severe impaired renal function (CC <30 ml / min).


Treatment Fazlodeksom should only be undertaken under the supervision of a physician who has experience of anticancer drugs.

Precautions recommended Fazlodeks patients with mild or moderate hepatic impairment.

We recommend caution when using Fazlodeksa in patients with severe impaired renal function (CC <30 ml / min).

Given the way the drug is recommended to use caution when applying Fazlodeksa patients with a bleeding tendency with thrombocytopenia or patients taking anticoagulants. Thromboembolism in women with advanced breast cancer occur frequently. This should be taken into account when appointing Fazlodeksa patients with risk of thromboembolism.

Effect Fazlodeksa on bone for prolonged use has not been established.

Given the mechanism of action of fulvestrant, we can not exclude the potential risk of developing osteoporosis.

Fazlodeks not be mixed with other drugs.

Use in Pediatrics

Data on the safety and efficacy in children and adolescents are not available.

Effects on ability to drive vehicles and management mechanisms

Effect Fazlodeksa driving ability and other mechanisms is negligible. Patients with symptoms of asthenia be careful when driving or other mechanisms.


Cases of overdose in humans is unknown.

Symptoms: In experimental animal studies, the introduction of fulvestrant high-dose effects were observed only, directly or indirectly associated with Antiestrogenic activity. Treatment: In cases of overdose recommended symptomatic therapy.

Drug Interactions

According to the study of the clinical interaction with midazolam fulvestrant does not inhibit the activity of CYP3A4. Data in vitro suggest that fulvestrant does not affect the activity of CYP1A2, 2C9, 2S19, and 2D6. Possible suppression of CYP2A6, 2S8 and 2E1 were not assessed.

In a study of the clinical interaction with rifampicin (inducer CYP3A4) and ketoconazole (an inhibitor of CYP3A4) have been found clinically significant changes in clearance of fulvestrant. Therefore, the appointment fulvestrant in combination with inducers, or inhibitors of CYP3A4 dose adjustment is required.

Terms and Conditions of storage

The drug should be stored out of reach of children protected from light at 2 ° to 8 ° C.

Shelf life - 4 years.


Composition, structure and packing

Coated tablets light brown, round, biconvex.

1 tab. cytisine 1.5 mg.

Excipients: lactose, microcrystalline cellulose, talc, magnesium stearate, Opadry II.

Clinico-pharmacological group: Drug for treatment of nicotine addiction.

Pharmacological action

H-holinomimetik. Stimulates nicotinic receptors of autonomic ganglia, reflexly stimulates respiratory center, causing the release of adrenaline hromafinnymi medullar cells of the adrenal glands, raises blood pressure.

Reduces nicotine dependence (due to the competitive relationship in the field of the same receptors and biochemical substrates, with which the body interacts nicotine). It changed the taste of smoking (making it unpleasant), reduces the desire to smoke and facilitates manifestation of withdrawal symptoms associated with smoking cessation.

The mechanism of action of cytisine similar to the mechanism of action of nicotine, which makes it possible to phase out smoking at the same time prevents the development of abstinence phenomena.


Data on pharmacokinetics is not available.

Nicotine addiction (to facilitate smoking cessation).

Dosage regimen

The drug is prescribed for 3 days to 1 tab. 6 times / day (2 h) in parallel reduce the number of cigarettes smoked. In the absence of the effect of the drug should be removed and after 2-3 months to begin a new course.

With the positive result of treatment should be continued as follows:

Frequency of treatment / Multiplicity / receiving dose

from 4 to 12 days to 1 tab. every 2.5 h 5 pi.

from 13 to 16 days for 1 tab. every 3 h 4 pi.

from 17 to 20 days to 1 tab. every 5 h 3 pi.

from 21 to 25 days to 1 tab. every 6-8 hours 1-2 tab.

Smoking should be discontinued no later than 5 days from start of treatment.

Side effect

On the part of the digestive system: changing tastes and appetite, dry mouth, abdominal pain, nausea, constipation, diarrhea.

From the side of the central nervous system: headache, dizziness, insomnia, drowsiness, increased irritability.

Since the cardiovascular system: a feeling of palpitations, a slight increase in blood pressure, tachycardia, chest pain, shortness of breath.

Other: myalgia, weight loss, increased sweating, allergic reactions.

Most adverse events are held independently.

Acute myocardial infarction;
unstable angina
recently transferred cerebral blood flow;
marked atherosclerosis;
bleeding from large vessels;
pulmonary edema;
peptic ulcer of the stomach and duodenum (phase exacerbation);
lactation (breastfeeding);
Hypersensitivity to the drug.

With care prescribers in schizophrenia, hromafinnyh adrenal tumors, gastroesophageal reflux, with coronary artery disease (including chronic heart failure), cerebrovascular disease, hyperthyroidism, peptic gastric ulcers, diabetes, renal and hepatic failure. Children under the age of 18 years and patients older than 65 years the drug should be used after careful evaluation of the ratio expected benefits and potential risks.

Pregnancy and lactation

Do not assign Tabex during pregnancy because of the potential risk of embryotoxicity in uncontrolled admission.

Do not take the drug during lactation (breastfeeding).

Application for violations of liver function

Be wary prescribers with hepatic failure.

Application for violations of renal function

With care prescribers in renal failure.


The drug should be used only if the patient has a serious and deliberate intention to quit smoking.

The patient should be warned that the use of the drug on the background of continued smoking can lead to nicotine poisoning.

Effects on ability to drive vehicles and management mechanisms

Acceptance of the drug did not cause changes in mental and physical condition of the patient, does not violate the ability to manage road and work with mechanisms.


Symptoms: nausea, vomiting, dilated pupils, weakness, tachycardia, convulsions, respiratory paralysis.

Treatment: gastric lavage, control heart rate, blood pressure, respiratory function, if necessary - the introduction of infusion solutions, anticonvulsive drugs, cardiac, analeptic and other symptomatic means.

Drug Interactions

The drug should not be used simultaneously with anti-TB drugs.

Terms and Conditions of storage

The drug should be stored in a dry place protected from light, away from children at or above 25 ° C. Shelf life - 2 years.


Method of production - tablets (bezyacheykovye outline package)

Pharmacotherapeutic group - antispasmodic

Pharmacological action

Ingredients - benzocaine 300 mg, 50 mg papaverine hydrochloride

Pain in the abdomen and pelvis
Pain localized in the upper abdomen
Symptoms and signs related to the digestive system and abdomen

The composition of the components


Pain in the stomach, smooth muscle spasms of the abdominal cavity.

Dosage regimen

Inward 1 tablet 2-3 times / day.

Side effects

Allergic reactions, nausea, constipation, drowsiness, sweating.


Hypersensitivity, AV block, children under 1 year.


Incompatible and inhibitors of monoamine oxidase (MAO).


Composition, structure and packing

The tablets are white, round, beveled edges, with the risk on one side, on one side risks stamped "4", on the other - "0", the second side of the tablet is smooth.

1 tab. propranolol hydrochloride 40 mg

Excipients: lactose monohydrate, potato starch, talc, sodium karboksimetilkrahmal (type A), gelatin, magnesium stearate, silicon dioxide highly dispersed.

20 pcs. - Blisters (3) - packs cardboard.

Clinico-pharmacological group:

Beta 1 -, beta 2-blocker

Registration № №: pi. 40 mg: 60 pcs. - P № 011665/01, 08.09.06

Pharmacological action

Nonselective beta-blocker. Possesses antianginal, antihypertensive and antiarrhythmic action. Selectively blocking β-adrenergic receptors (75% β1-adrenergic receptors and 25% β2-adrenergic receptors), decreases catecholamines stimulated formation of cAMP from ATP, resulting in reduced intracellular calcium intake has a negative chrono-, Drome, BATM-and inotropic effects (slows heart rate, depresses conduction and excitability, reduces myocardial contractility).

In the first 24 hours of the drug increases TPVR (as a result of reciprocal increase in the activity of α-adrenoceptor stimulation and removal of β2-adrenoceptor vessels of skeletal muscle), but after 1-3 days, returned to baseline, and at long assignment decreases.

Antihypertensive effect of the drug is associated with a decrease in cardiac output, decrease in sympathetic stimulation of peripheral blood vessels, decreased activity of the renin-angiotensin system (counts in patients with initial hypersecretion of renin), decrease the sensitivity of baroreceptors of the aortic arch (not going to enhance their activity in response to BP decrease) and the impact on the CNS. Antihypertensive effect will stabilize by the end of 2 weeks localizer destination.

Antianginal is due to reduced myocardial oxygen demand (due to the negative chronotropic and inotropic effect). The decrease in heart rate leads to a lengthening of diastole and improve myocardial perfusion. Due to increasing end-diastolic pressure in the left ventricle and increase the tension of muscle fibers of the ventricles can increase oxygen demand, especially in patients with chronic heart failure.

Antiarrhythmic effect is due to the elimination of arrhythmogenic factors (tachycardia, increased activity of the sympathetic nervous system, increase of cAMP, arterial hypertension), decrease in the rate of spontaneous excitation of sinus and ectopic pacemakers and slowing AV-holding. Inhibition of the pulses observed mainly in the antegrade and to a lesser extent in the retrograde direction through the AV-node and on additional routes. By reducing myocardial oxygen demand decreases the severity of myocardial ischemia, postinfarction mortality may also decrease due to antiarrhythmic action.

The ability to prevent the development of headache of vascular origin due to a decrease in severity of cerebral arteries due to expansion of β-adrenoceptor blockade vessels, inhibition of catecholamines induced platelet aggregation and lipolysis, reduction of platelet adhesiveness, prevention of activation of blood clotting factors during the release of adrenaline, stimulation of oxygen to the tissues and a decrease in secretion renin.

Reduction of tremor during treatment with propranolol may be due to blockade of β2-adrenergic receptors.

Improves Atherogenic properties of blood. Promotes uterine contractions (spontaneous and drug-induced, stimulating the myometrium). Increases tone of the bronchi.



After ingestion is absorbed quickly and adequately (90%). Cmax plasma levels achieved after 1-1.5 h. Bioavailability after a single oral administration of 30-40% (the effect of "first pass" through the liver microsomal oxidation), Propafenone - increases (formation of metabolites that inhibit liver enzymes), its magnitude depends on the nature of food and the intensity of hepatic blood flow.


It has high lipophilicity, accumulate in the tissue of the lungs, brain, kidneys and heart. " Penetrates through the blood-brain and placental barriers in breast milk. Relationship to plasma proteins - 90-95%. Vd - 3-5 L / kg.


Biotransformiruetsya in the liver by glyukuronirovaniya. Falls into the bile into the intestine, deglyukuroniziruetsya and reabsorbed.


Relatively rapidly excreted from the body. T1 / 2 - 3-5 hours on the background of the introduction of exchange rate may grow up to 12 hours with urine - 90%, unchanged - less than 1%. Not deleted at hemodialysis.

arterial hypertension
unstable angina (excluding Prinzmetal angina)
sinus tachycardia (including in hyperthyroidism)
atrial tachyarrhythmia;
supraventricular and ventricular extrasystoles
prevention of myocardial infarction (systolic blood pressure above 100 mm Hg)
essential tremor
migraine (prevention of attacks)
as symptomatic treatment of thyrotoxicosis and hyperthyrosis crisis (when intolerance thyreostatic drugs)
sympatho-adrenal crises against the background of diencephalic syndrome

Dosage regimen

Tablets, taken orally, before a meal, without chewing, and squeezed a small amount of liquid.

When hypertension appoint 40 mg 2 times / day. In case of insufficient severity of the hypotensive effect of daily dose increased to 120 mg (40 mg 3 times / day) or up to 160 mg (80 mg 2 times / day). The maximum daily dose - 320 mg.

In angina, cardiac arrhythmia initial daily dose is 60 mg (20 mg 3 times / day), then the daily dose increased to 80-120 mg, divide it into 2-3 reception. The maximum daily dose - 240 mg.

To prevent migraines, as well as essential tremor drug is prescribed in an initial dose of 120 mg (40 mg 3 times / day).

To prevent recurrent myocardial infarction therapy Obzidanom should begin between 5 th and 21 th day after myocardial infarction. The drug is prescribed at a dose of 120 mg (40 mg 3 times) per day for 2-3 days, and then continue taking the drug at 80 mg 2 times / day. You can assign Obzidan a daily dose of 180-240 mg in 2-3 reception.

In hyperthyroidism (symptomatic treatment) Obzidan appoint 40 mg 3-4 times / day.

In case of violation of renal function is necessary to reduce the initial dose or increase the interval between doses of the drug.

If abnormal liver function should reduce the dose of the drug.

Side effect

Since the cardiovascular system: sinus bradycardia, AV-block, heart failure, palpitation, myocardial conduction disturbances, arrhythmias, lowering blood pressure, orthostatic hypotension, chest pain, spasm of peripheral arteries, cold extremities.

On the part of the digestive system: dry mouth, nausea, vomiting, diarrhea, constipation, pain in the epigastric region, abnormal liver function, changes in taste.

From the side of the central nervous system and peripheral nervous system: Rarely - headache, insomnia, nightmares, asthenia syndrome, reducing the capacity for rapid mental and motor reactions, agitation, depression, paresthesia, fatigue, weakness, dizziness, drowsiness, confusion, or momentary loss of memory, hallucinations, tremor.

On the part of the respiratory system: rhinitis, nasal congestion, dyspnea, bronchospasm, laryngism.

From the Metabolic: hypoglycemia (in patients with diabetes mellitus type 1), hyperglycemia (in patients with diabetes mellitus type 2).

From the sensory organs: eye dryness of the mucous membrane (a decrease of secretion of tear fluid), the violation of visual acuity, keratoconjunctivitis.

On the part of the reproductive system: reduction of libido, reduced potency.

Dermatological reactions: alopecia, exacerbation of psoriasis, sweating, flushing of skin, rash, psoriazopodobnye skin reactions.

On the part of the endocrine system: reduction of thyroid function.

Allergic reactions: skin rash, itching.

From the laboratory parameters: agranulocytosis, leukopenia, thrombocytopenia, increase in liver transaminases and bilirubin.

Other: muscle weakness, back pain or joint pain, chest pain, withdrawal syndrome.

AV-block II and III degree
sinoatrial block
sinus bradycardia
hypotension (systolic blood pressure below 90 mm Hg)
uncontrolled chronic heart failure stage IIB-III
acute heart failure
acute myocardial infarction (systolic blood pressure below 100 mm Hg)
cardiogenic shock
pulmonary edema
sick sinus syndrome
Prinzmetal angina
cardiomegaly (with no signs of heart failure)
vasomotor rhinitis
occlusive peripheral vascular disease (complicated with gangrene, a symptom of intermittent claudication or pain at rest)
diabetes mellitus
metabolic acidosis (including diabetic ketoacidosis)
bronchial asthma
propensity to bronhospasticheskim reactions
chronic obstructive pulmonary disease (including a history)
pheochromocytoma (without the simultaneous use of alpha-blockers)
spastic colitis
simultaneous reception of antipsychotic drugs and anxiolytic (chlorpromazine, trioxazine, etc.)
simultaneous reception with MAO inhibitors
Lactation (breastfeeding)
Hypersensitivity to the drug

Precautions should be prescribed drug in AV-blockade of I degree, hepatic and / or renal failure, hyperthyroidism, myasthenia gravis, chronic cardiac insufficiency stage I-IIA, pheochromocytoma, psoriasis, allergic reactions, a history of Raynaud's syndrome, pregnancy, elderly patients, children and adolescents under the age of 18 years (the efficacy and safety have not been established).

Application of pregnancy and breastfeeding

Application Obzidana during pregnancy is possible only when the intended benefits to the mother outweighs the potential risk to the fetus. If you want to use in this period should be careful monitoring of the fetus, because Reception Obzidana during pregnancy can cause intrauterine growth retardation, hypoglycemia and bradycardia in a fetus. For 48-74 hours before delivery Obzidan should be abolished.

Application Obzidana contraindicated during lactation. If necessary, its use in this period, breast-feeding should be discontinued.

Application for violations of liver function

If abnormal liver function should reduce the dose of the drug.

Application for violations of renal function

In case of violation of renal function is necessary to reduce the initial dose or increase the interval between doses of the drug.


In appointing Obzidana should systematically monitor the heart rate and blood pressure (at the beginning of treatment - every day, then 1 every 3-4 months), ECG.

In elderly patients should be monitoring of kidney function (1 every 4-5 months).

In the case of elderly patients increasing bradycardia (less than 50 bpm), arterial hypotension (systolic blood pressure below 100 mm Hg), AV-blockade, bronchospasm, ventricular arrhythmias, severe disturbances of liver function and / or kidneys, necessary to reduce the dose or stop treatment.

It should teach the patient methods of calculating heart rate and instruct on the need of medical advice in the heart rate below 50 bpm.

It is recommended to discontinue therapy Obzidanom in the development of depression caused by his reception.

Patients who use contact lenses should be aware that during the treatment Obzidanom may decrease production lacrimal fluid.

Before the appointment Obzidana patients with heart failure (early stage) should be used with cardiac glycosides and / or diuretics.

Treatment of ischemic heart disease and resistant hypertension should be prolonged. Receiving Obzidana possible within a few years.

Termination of treatment carried out gradually, under medical supervision, abrupt withdrawal may intensify myocardial ischemia, pain in angina, worse exercise tolerance. Cancel Obzidana conducted within 2 weeks or more, gradually reducing the dose (by 25% every 3-4 days).

In patients with diabetes using the product under the control of blood glucose (1 every 4-5 months). In appointing Obzidana patients receiving hypoglycemic medications should be careful, because during long breaks in food intake can develop hypoglycemia. And its such symptoms as tachycardia or tremor will be blacked out due to the action Obzidana. Patients should be warned that the main symptom of hypoglycemia during treatment Obzidanom is increased sweating.

Precautions should be appointed Obzidan with hypoglycemic agents (the risk of hypoglycemia in insulin therapy and hyperglycemia - at the intake of oral hypoglycemic funds).

When thyrotoxicosis Obzidan may mask certain clinical signs of hyperthyroidism (eg tachycardia). Abrupt withdrawal of the drug is contraindicated in patients with thyrotoxicosis, as can intensify symptoms.

At the same time taking clonidine its reception can be terminated only after a few days after the cancellation Obzidana.

When pheochromocytoma Obzidan appoint only in combination with alpha-blockers.

Drugs that reduce the supply of catecholamines (eg reserpine) may enhance the action Obzidana, so patients taking a combination of these drugs should be under constant medical supervision in order to identify arterial hypotension and bradycardia.

The treatment should be avoided Obzidanom in / introduction of verapamil, diltiazem.

A few days before the general anesthesia with chloroform or ether must stop taking the drug (increased risk of depression of the myocardium and the development of arterial hypotension).

It should cancel the drug before the study of blood and urine catecholamines, normetanephrine and vinilamidalnoy acid, antinuclear antibody titers.

In patients who abuse tobacco, efficiency Obzidana reduced.

During treatment Obzidanom not recommended to take alcohol (probably a sharp decline in BP).

During the reception Obzidana should avoid the use of natural licorice, food, rich in protein, can increase the bioavailability of propranolol.

Use in Pediatrics

Efficacy and safety of Obzidana in children and adolescents under the age of 18 is not installed.

Effects on ability to drive vehicles and management mechanisms

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


Symptoms: bradycardia, dizziness or fainting, decrease blood pressure, arrhythmia, shortness of breath, cyanosis of nails of fingers or palms, convulsions, cardiac arrest (in into / in the introduction).

Treatment: gastric lavage, the appointment of activated carbon (ingestion), with violations of AV-conduction - in / injected 1-2 mg of atropine, epinephrine, at low efficiency exercise staging temporary pacemaker with ventricular arrhythmia - lidocaine (Class IA drugs are not applicable), with arterial hypotension (the patient must be in a supine position with a lowered head end of bed), if there are no signs of pulmonary edema in / injected plazmozameschayuschie solutions for inefficiency - epinephrine, dopamine, dobutamine, with convulsions - in / diazepam; with bronchospasm - inhalation or parenteral beta-adrenostimulyatorov.

Drug Interactions

With simultaneous application of Obzidana with MAO inhibitors there is a considerable strengthening of the hypotensive action, so this combination is contraindicated, interruption in the treatment between the intake of MAO inhibitors and Obzidana must be at least 14 days.

With the simultaneous use of diuretics, reserpine, hydralazine and other antihypertensives, as well as the hypotensive effect of ethanol Obzidana increases.

The hypotensive effect Obzidana weaken GCS, NSAIDs (sodium retention and blocking prostaglandin synthesis by the kidneys), estrogens (sodium retention) and MAO inhibitors.

Obzidan while the application increases the effects thyreostatic and uterotoniziruyuschih drugs, reduces effect of antihistamines.

At simultaneous application with Obzidanom amiodarone, verapamil and diltiazem increased the severity of negative chrono-, foreign-and dromotropic actions.

When in / introduction of iodine radiopaque drugs on a background of reception Obzidana increases the risk of anaphylactic reactions.

Phenytoin at a / in the introduction, means for inhalation anesthesia (derivatives of hydrocarbons), while applying to increase the severity Obzidanom cardiodepressive action and the probability of reducing blood pressure.

Obzidan while the application modifies the effectiveness of insulin and oral hypoglycemic drugs, masking the symptoms of developing hypoglycemia (tachycardia, increased BP).

Cardiac glycosides, methyldopa, reserpine, and guanfatsin, antiarrhythmics, while admission to Obzidanom increase the risk of development or worsening of bradycardia, AV-blockade, cardiac arrest and heart failure.

Nifedipine while applying to Obzidanom can lead to a significant reduction in blood pressure.

Obzidan prolongs the action nondepolarizing muscle relaxants and anticoagulant effect of coumarins.

Three-and tetracyclic antidepressants, antipsychotic drugs (neuroleptics), ethanol, sedatives and sleeping pills, while applying to Obzidanom enhance the inhibitory effect on the CNS.

Negidrirovannye ergot alkaloids when used with a Obzidanom increase the risk of disorders of peripheral circulation.

Application Obzidana increases the likelihood of severe systemic reactions (anaphylaxis) against the introduction of allergens used for immunotherapy or skin tests.

Pharmacokinetic interaction

Cimetidine increases bioavailability of propranolol.

Propranolol increases the concentration of lidocaine in blood plasma, reduces the clearance of theophylline.

In case of simultaneous appointment of propranolol with the derivatives of phenothiazine concentrations of both drugs in blood plasma increased.

Propranolol reduces the clearance of xanthine (except difillina).

Sulfasalazine increases the concentration of propranolol in the blood plasma (inhibits metabolism), rifampicin shortens the half-life of propranolol.

Terms and Conditions of storage

List B. preparation should be kept in the dark, away from children at a temperature of 15 ° to 25 ° C. Shelf life - 5 years.

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Drug prescription.


Composition, structure and packing

Soft gelatin capsules, oval, size, number 3, light brown color, with red inscription "N20"; contents of capsules - viscous solution from light yellow to orange-yellow color.

1 capsule. vinorelbina tartrate 27.7 mg, which corresponds to the content vinorelbina 20 mg.

Excipients: ethanol anhydrous, purified water, glycerol, macrogol 400.

The composition of the shell capsules: gelatin, glycerol 85%, anidrisorb 85/70 (D-sorbitol and 1,4-sorbitan), triglycerides srednetsepochechnye PHOSAL 1953 MST (phosphatidylcholine, glycerides, ethanol), iron oxide red (E172), iron oxide yellow ( E171

Soft gelatin capsules, oblong, size, number 4, pink, red-labeled "N30"; contents of capsules - viscous solution from light yellow to orange-yellow color.

1 capsule. vinorelbina tartrate 41.55 mg, which corresponds to the content vinorelbina 30 mg.

Excipients: ethanol anhydrous, purified water, glycerol, macrogol 400.

The composition of the shell capsules: gelatin, glycerol 85%, anidrisorb 85/70 (D-sorbitol and 1,4-sorbitan), triglycerides srednetsepochechnye PHOSAL 1953 MST (phosphatidylcholine, glycerides, ethanol), iron oxide red (E172), iron oxide yellow ( E171

Concentrate for solution for infusion is transparent, from colorless to pale yellow.

1 ml vinorelbina tartrate 13.85 mg, which corresponds to the content vinorelbina base 10 mg.

Excipients: Water d / and nitrogen (inert gas).

Concentrate for solution for infusion is transparent, from colorless to pale yellow.

5 ml vinorelbina tartrate 69.25 mg, which corresponds to the content vinorelbina base 50 mg.

Excipients: Water d / and nitrogen (inert gas).

Clinico-pharmacological group: The antitumor drug.

Pharmacological action

The antitumor drug from the group vinkaalkaloidov (pink periwinkle alkaloid obtained by semi-synthetic). The drug blocks the mitosis of cells at metaphase G2-M, causing cell death during interphase or during the subsequent mitosis. At the molecular level affect the dynamic equilibrium of tubulin in the microtubule apparatus of the cell. Navelbin inhibits polymerization of tubulin by binding predominantly to the mitotic microtubules, but in higher concentrations also affects the axonal microtubules. Induction of helix tubulin under the influence Navelbina less pronounced than with vincristine.


Absorption and distribution

After ingestion rapidly absorbed from ZhKT.Smax vinorelbina achieved through 1.5-3 h. The absolute bioavailability averaging 40%. Eating does not affect the degree of suction.

After i / v administration kinetics vinorelbina a three-phase exponential process.

Binding to plasma proteins is 13.5%. Intensive contacts with cells of blood and especially platelets (78%). Well into the tissue and delayed them for a long time. High concentrations vinorelbina determined in the spleen, liver, kidneys, lungs and thymus, moderate - in the heart and muscles, minimum - in the adipose tissue and bone marrow. Concentration in the lungs is 300 times higher than the concentration in plasma. Do not cross the BBB.

Metabolism and excretion

Biotransformiruetsya in the liver, mainly under the influence of CYP3A4 isoenzyme with the formation of several metabolites, mostly determined in the blood is diatsetilvinorelbin which retains antitumor activity. Derive mainly from the bile. The average T1 / 2 in the terminal phase is 40 h (27.7-43.6 h).

Pharmacokinetics in special clinical situations

Pharmacokinetic parameters Navelbina (introduced in a dose of 20 mg/m2 weekly) does not depend on the age of patients and did not change with moderate or severe hepatic insufficiency.

non small cell lung cancer of the lung;
breast cancer;
prostate cancer resistant to hormone therapy (in combination with low doses of GCS for oral).

Dosage regimen

Navelbin used as a monotherapy and in combination with other anticancer agents. When choosing the dose and mode of administration in each individual case should be referred to special literature.

Concentrate Navelbina introduced strictly in / as the 6-10 minute infusion.

The capsules are inside entirely, drinking water, not liquid and not rassasyvaya them in his mouth.

In monotherapy the usual dosage for a / in the introduction of 25-30 mg/m2 body surface once a week. Navelbin diluted in 0.9% sodium chloride or 5% dextrose to a concentration of 1.0-2.0 mg / ml (average 50 ml). After drug administration the vein should be flushed by introducing an additional minimum of 250 ml 0.9% sodium chloride or 5% dextrose.

For patients with body surface area 2 m2 and a single dose for Navelbina in / introduction must not exceed 60 mg.

Recommended single initial dose Navelbina Oral 60 mg/m2 body surface once a week. After receiving the third dose is recommended to increase to 80 mg/m2.

If the number of neutrophils did not decrease less than 500 cells / mm, or more than one was observed to reduce the number of neutrophils in the range from 500 to 1000/mkl within three weeks of Navelbina dose of 60 mg/m2 (in accordance with the above recommendations), we can again increase the dose from 60 to 80 mg/m2 per week.

Recommended doses Navelbina Oral depending on body surface area (BSA) are given in the following table.

Body surface area (m2) 60 mg/m2 80 mg/m2 dose (mg) per week

From 0.95 to 1.0 60 80

From 1.05 to 1.14 70 90

From 1.15 to 1.24 70 100

From 1.25 to 1.34 80 100

From 1.35 to 1.44 80 110

From 1.44 to 1.54 90 120

From 1.55 to 1.64 100 130

From 1.65 to 1.74 100 140

From 1.75 to 1.84 110 140

From 1.85 to 1.94 110 150

1.95 and more than 120 160

For patients with a BSA 2 m 2 and the more general single dose Navelbina Oral should never exceed 120 mg per week in the appointment of the drug in a dose of 60 mg/m2 and 160 mg per week at a dose of 80 mg/m2.

Application Navelbina inside at doses of 60 mg/m2 and 80 mg/m2 corresponds to / in the introduction Navelbina at doses of 25 mg/m2 and 30 mg/m2.

When chemotherapy dose and frequency of administration Navelbina (as in in / in the introduction, and ingestion) depend on the specific program of anticancer therapy.

By reducing the number of neutrophils, or platelets less 1500/mkl least 75 000/mkl (with a / in the introduction), or less than 100 000/mkl (ingestion), the next administration or ingestion Navelbina set aside for 1 week. If, due to hematological toxicity had to abstain from 3 weekly injections or a drug-use Navelbina be discontinued.

Patients with severe hepatic insufficiency Navelbin be used with caution in doses, decreased by 33%.

Safety and effectiveness in Navelbina in children has not been studied.

Special correction Navelbina dosing regimen in the elderly is not required.

Side effect

The following side effects occurred more frequently than in isolated cases. We used the following criteria for evaluating the frequency of occurrence of undesirable effects: very common (> 1 / 10), frequently (> 1 / 100, 1 / 10), sometimes (> 1 / 1000, 1 / 100), rare (> 1 / 10000, 1 / 1000), rarely (1 / 10000).

On the part of the hemopoietic system: very often - neutropenia, anemia, thrombocytopenia, secondary infections accession against the oppression of bone marrow hematopoiesis and often - fever (38 ° C) in the presence of neutropenia, sometimes - sepsis, septicemia, very rarely - is complicated by septicemia, in some cases leading to death. The smallest number of neutrophils observed at 7-10 days of therapy, recovery occurs in the next 5-7 days. Cumulation gematotoksichnosti not observed.

On the part of the peripheral nervous system: very often - paresthesia, hyperesthesia, reduction or loss of deep tendon reflexes, and often - a weakness in the legs, sometimes - hard paresthesia with sensory and motor symptoms are usually reversible.

Since the cardiovascular system: sometimes - increase or decrease blood pressure, hot flushes and cold extremities; rare - CHD (angina, myocardial infarction), expressed as hypotension, collapse, very rarely - tachycardia, palpitations, heart rhythm disturbances.

In the respiratory system: sometimes - shortness of breath, bronchospasm, rarely - interstitial pneumonia (in combination therapy with mitomycin), acute respiratory distress syndrome.

On the part of the digestive system: very often - nausea, vomiting, stomatitis, constipation, diarrhea, transient increase in liver function tests (ALT, ACT); rarely - pancreatitis, raising the level of bilirubin, paresis of the intestine.

On the part of the immune system: rare - anaphylactic shock, angioedema.

Dermatological reactions: often - alopecia, rarely - skin rashes.

Local reactions: often - pain / burning or redness at the injection site, change in color of the veins, phlebitis, with extravasation - Cellulite possible - necrosis of the surrounding tissues.

Other: often - fatigue, myalgia, arthralgia, fever, pain, various locations, including chest pain, pain in the lower jaw and in the field of tumor formation; rare - hyponatremia, very rarely - hemorrhagic cystitis and the syndrome of inappropriate secretion of ADH.

number of neutrophils less 1500/mkl;
platelet count less than 75 000/mkl (for in / in the introduction) and less than 100 000/mkl (Oral);
serious infectious disease during the beginning of therapy or deferred in the past two weeks;
marked deficiency of liver function, not related to the neoplastic process;
need for constant oxygen therapy in patients with tumors of the lung;
diseases and conditions that lead to a decrease in absorption from the gastrointestinal tract (for oral);
Pregnancy - Lactation (breastfeeding);
Hypersensitivity to the drug and other vinkaalkaloidam.

Be wary prescribers with respiratory failure, inhibition of bone marrow hematopoiesis (including after previous chemotherapy or radiation therapy), constipation, or intestinal obstruction phenomena in history, a history of neuropathy.

Pregnancy and lactation

Navelbin contraindicated during pregnancy and lactation (breastfeeding).

Application for violations of liver function

Patients with severe hepatic insufficiency Navelbin be used with caution in doses, decreased by 33%.

Application for violations of renal function

In case of violation of renal function is necessary to monitor the patient's condition.


Treatment Navelbinom should be under the supervision of a physician who has experience working with anticancer agents.

In marked abnormal liver function Navelbina doses should be reduced by 33%.

In case of violation of renal function should be monitored the patient's condition.

If signs of neurotoxicity of 2 or more degrees Navelbina use should be discontinued.

If you have shortness of breath, cough, or hypoxia of unknown etiology should examine the patient to avoid pulmonary toxicity.

When extravasation of the drug infusion should be stopped immediately, the remaining dose injected into another vein.

In the case of nausea or vomiting after taking the capsules Navelbina again the same dose should not be accepted.

During and for at least three months after cessation of therapy, you must use reliable methods of contraception.

After contact with the active substance in the oral cavity is recommended to rinse your mouth with water or any saline solution.

In case of contact Navelbina in their eyes should be abundantly and thoroughly rinse with water.

Since the substance is formulated sorbitol, Navelbin should not be used in patients with hereditary fructose intolerance.

Monitoring of laboratory parameters

Treatment with conduct under strict hematological control, determining the number of leukocytes, neutrophils, platelets and hemoglobin levels before each regular injection or ingestion. By reducing the number of neutrophils less 1500/mkl and / or platelets less than 75 000/mkl (for in / in the introduction) or less 100 000/mkl (Oral) application for another dose of the drug to postpone the normalization parameters simultaneously monitor the patient's condition.


Symptoms: suppression of bone marrow function, neurotoxic reactions.

Treatment: In case of overdose the patient should be hospitalized; spend symptomatic therapy with careful monitoring of functions of vital organs. The specific antidote is known.

Drug Interactions

In a joint application with other cytostatic possible mutual exacerbation of side effects, in the first place - myelosuppression.

When combined with the use of mitomycin C may develop acute respiratory failure.

In the application in conjunction with paclitaxel increases the risk of neurotoxicity.

Application on the background radiation therapy leads to radiosensitization. Application Navelbina after radiotherapy can lead to the reinvention of the light reactions.

The simultaneous use of the drug with inducers and inhibitors of cytochrome P450 isoenzymes may lead to a change in the pharmacokinetics vinorelbina

Terms and Conditions of storage

Concentrate for solution for infusion should be stored out of reach of children, protected from light at 2 ° to 8 ° C. Capsules should be stored out of reach of small children at a temperature of 2 ° to 8 ° C.

After further dilution of concentrate its physical and chemical stability persists for 8 days at room temperature (20 ° ± 5 ° C) or in the refrigerator (2 ° to 8 ° C).

From microbiological point of view of the drug after dilution should be used immediately. If the drug was not introduced immediately, the health worker assumes responsibility for the conditions and duration of storage before administration. Typically, the duration of such storage shall not exceed 24 hours at a temperature of 2 ° to 8 ° C, except when the dilution was carried out in controlled and validated aseptic conditions.

Expiration date concentrate - 3 years. After further dilution of the drug with saline or glucose solution shelf life of 24 h at room temperature.

Expiration capsules - 2.5 years.


Composition, structure and packing

Concentrate for solution for infusion is transparent or slightly opalescent, colorless or pale yellow. 1 ml 1 vial. rituximab 10 mg 100 mg. Excipients: sodium citrate dihydrate, polysorbate 80, sodium chloride, water, d / and hydrochloric acid or sodium hydroxide.

Concentrate for solution for infusion is transparent or slightly opalescent, colorless or pale yellow. 1 ml 1 vial. rituximab 10 mg 500 mg. Excipients: sodium citrate dihydrate, polysorbate 80, sodium chloride, water, d / and hydrochloric acid or sodium hydroxide.

Clinico-pharmacological group: The antitumor drug. Monoclonal antibodies.

Pharmacological action

Medical immuno-biological product, is a chimeric monoclonal antibody mouse / human, which specifically binds to the transmembrane antigen, CD20. This antigen is located on the pre-B lymphocytes and mature B-lymphocytes, but not on hematopoietic stem cells, pro-B cells, normal plasma cells, cells of other tissues, and is expressed in more than 95% of cases with B-cell non-Hodgkin's Lymphomas . After binding to CD20 antibody is not internalized and no longer deal with the cell membrane into the extracellular space. CD20 does not circulate in plasma in the form of free antigen and therefore does not compete for binding to antibodies. Rituximab binds to CD20 antigen on B-lymphocytes and initiates immunological reactions that mediate lysis of B-cells.

Possible mechanisms of cell lysis include complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity and induction of apoptosis. Rituximab sensitizes the line of B-cell lymphoma rights to the cytotoxic action of some chemotherapeutic drugs in vitro. The number of B cells in peripheral blood after the first injection of the drug is reduced below normal, and begins to recover in patients with hematological malignant diseases after 6 months, reaching normal values by 9-12 months after completion of therapy.

In patients with rheumatoid arthritis duration of reducing the number of B-cells varies, most patients follow prescribed treatment until full recovery of their number. Antihimernye antibodies were detected in 1.1% (4 out of 356) examined patients with non-Hodgkin's lymphoma and in 10% - with rheumatoid arthritis. Pharmacokinetics Non-Hodgkin's lymphoma in patients with recurrent c B-cell lymphoma, rituximab concentration in the serum and its T1 / 2 increases with increasing dose. After a 1-y / v infusion at a dose of 375 mg/m2 T1 / 2 of rituximab was 76.3 h after the 4 th infusion - 205.8 hours after Cmax 1-y infusion of 205.6 mg / ml after the 4 th infusion - 464.7 ug / ml, plasma clearance - 0.0382 L / h and 0.0092 L / h, respectively.

Individual differences in serum concentrations of the drug rather pronounced. With effective treatment, serum concentration of rituximab was significantly higher. The concentration of the drug negatively correlates with tumor burden. Traces of rituximab can be found in the body for 3-6 months after the last infusion.

In patients with diffuse large cell lymphoma rituximab serum concentrations comparable to those in patients with non-Hodgkin's lymphoma low-grade or follicular, receiving the same dose. Rheumatoid arthritis after two / v infusion of 1000 mg at 2-week break Cmax rituximab - 369 ug / ml, mean T1 / 2 - 19.2-20.8 days, mean systemic clearance - 0.23 l / d and Vd in the equilibrium state - 4.6 l .

Pharmacokinetics in special clinical situations

Vd and clearance of rituximab, adjusted for body surface area in men is somewhat higher than in women; correct dose of rituximab is not required. The data on pharmacokinetics in patients with renal and hepatic insufficiency are absent.


Non-Hodgkin's lymphoma:
recurrent or resistant to chemotherapy-cell, CD20-positive non-Hodgkin's lymphoma low-grade or follicular;
follicular lymphoma, stage III-IV in combination with chemotherapy scheme CVP in previously untreated patients;
follicular lymphoma, as maintenance therapy after response to induction therapy;
CD20-positive diffuse large non-Hodgkin's lymphoma, in combination with chemotherapy CHOP scheme.

Rheumatoid arthritis (active form) in adults in combination with methotrexate in case of intolerance or inadequate response to current modes of therapy involving one or more inhibitors of tumor necrosis factor (TNF-α).

Dosage regimen

The standard dosing regime Enter in / by infusion (slow), via a separate catheter, a dose of 375 mg/m2, 1 times a week. You can not enter in / bolus or as a / v injection. Recommended initial velocity of the first infusion of 50 mg / h, in the future it may be increased to 50 mg / h every 30 minutes, bringing up to a maximum speed - 400 mg / h. Subsequent infusions can be started from 100 mg / h and increase it to 100 mg / h every 30 min to a maximum speed of 400 mg / h. Before each infusion of MabThera should hold premedication (analgesic / antipyretic such as paracetamol, antihistamine, such as diphenhydramine).

If Mabtera not used in combination with CHOP or CVP chemotherapy in the sedation also include corticosteroids. Correction dose during treatment reduces the dose of rituximab is not recommended. When MabThera is introduced in combination with chemotherapy scheme CHOP or CVP, reducing the dose of chemotherapeutic drugs is carried out in accordance with standard recommendations.

Non-Hodgkin's lymphoma of low-grade or follicular.

Initial therapy: monotherapy in adults - 375 mg/m2 1 times per week for 4 weeks.

In combination with CVP (cyclophosphamide, vincristine, prednisolone): 375 mg/m2, on the first day of the cycle of chemotherapy after i / v administration of corticosteroids as part of a scheme CVP; 8 cycles (cycle - 21 days). Re-use in case of recurrence: patients who responded to the first course of therapy - 375 mg/m2 1 times per week for 4 weeks. Maintenance therapy: After the response to induction therapy administered in a dose of 375 mg/m2 1 time in 3 months, not exceeding 2 years or until disease progression.

Diffuse large non-Hodgkin's lymphoma.

In combination with chemotherapy scheme CHOP: 375 mg/m2, on the first day of each cycle of chemotherapy, 8 cycles, after i / v administration of corticosteroids. Other components of the circuit CHOP (cyclophosphamide, doxorubicin, and with vincristine) are introduced after the appointment of MabThera.

Rheumatoid arthritis

Initial therapy: prescribe a dose of 1000 mg / to drip slowly for 30 minutes to / in the introduction of methylprednisolone 100 mg, 1 every 2 weeks, a course of treatment - 2 infusion. Re-application is possible within 6 -12 months after the first course of therapy: 1000 mg 1 every 2 weeks, treatment - 2 infusion.

Patients older than 65 years of dose correction is required.

Terms of cooking and storage solution

Needed drug type in aseptic conditions and are bred to the calculated concentration (1-4 mg / ml) in infusion bottles (package) with a 0.9% solution of sodium chloride injection or 5% dextrose (solutions must be sterile and apyrogenic). To mix gently invert the vial (package) to avoid foaming. Before the introduction of the solution must be inspected for absence of impurities or discoloration. Since Mabtera not contain preservatives, the prepared solution should be used immediately.

The prepared infusion solution

MabThera is stable for 12 h at room temperature or for up to 24 hours at a temperature of 2 ° to 8 ° C. The physician responsible for the preparation conditions and storage time of the prepared solution before use.

Treatment effectiveness

Non-Hodgkin's lymphoma of low-grade or follicular


Initial therapy, 4 weeks. In patients with relapsed or resistant to chemotherapy of B-cell non-Hodgkin's lymphoma, low-grade or follicular, MabThera received a dose 375 mg/m2 as a 4 / 1 by infusion once a week, the total frequency of remission was 48% complete remission - 6% , partial remission - 42%. The median time to disease progression - 13 months. Total frequency of remission in patients with histological subtypes of tumors, C and D (classification IWF) was higher than with subtype A (58% and 12%, respectively) in patients with the largest tumor focus diameter of less than 5 cm higher than the diameter the focus of more than 7 cm (53% and 38%) and in patients with relapsed himiochuvstvitelnym - higher than himioustoychivym (duration of remission less than 3 months) 53% and 36%, respectively. Total frequency of remission in patients after autologous bone marrow transplantation 78% compared with 43% in patients without bone marrow transplantation. The frequency of therapy response MabThera does not correlate with age, sex, degree of malignancy, a massive defeat, the localization of lesions and the level of LDH. But obtained a statistically significant correlation between the frequency response and bone marrow: 40% of patients with bone marrow involvement responded to therapy compared with 59% of patients without bone marrow involvement (p = 0.0186). Initial therapy for 8 weeks.

Patients with relapsed or himioustoychivoy-cell non-Hodgkin's lymphoma low-grade or follicular common answer is 57%, median times to disease progression in response to therapy is 19.4 months (range 5.3-38.9 months). Initial treatment for the disease with bulky disease, 4 weeks.

In patients with relapsed or himioustoychivoy B-cell non-Hodgkin's lymphoma low-grade or follicular with a massive defeat (the diameter of the tumor core ≥ 10 cm) overall response was 36% and median time to disease progression in response to therapy - 9.6 months (range 4.5-26.8 months). Re-treatment, 4 weeks. The frequency of remission in re-treated patients is comparable to that in the first course of therapy.

In patients with relapsed or himioustoychivoy B-cell non-Hodgkin's lymphoma of low-grade or follicular with an objective response to previous treatment with MabThera her reappointment overall response to treatment reached 38%, median time to disease progression among respondents - 17.8 months.

The combination with CVP (R-CVP) Combined therapy R-CVP (Mabtera 375 mg/m2 on the first day of each cycle, cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2 to 2 mg / day for the first day of the cycle, and prednisolone 40 mg / m2/sut, 1-5 day, every 3 weeks, with 8 cycles), the main criteria of efficiency - reducing the risk of lack of therapeutic response to the 67% increase in time to the development of ineffective treatment from 6.7 months to 25.9 months (p <0.0001).

Frequency response (complete response, unconfirmed complete response, partial response) in group R-CVP was: 80.9% compared with 57.2% (p <0.0001). After 18 months after the start of therapy the median duration of treatment response was not achieved in the group R-CVP and was 9.8 months in the group CVP (p <0.0001). The risk of recurrence decreased by 70% in the appointment of R-CVP (p <0.0001). Frequency of survival without events after 12 months of therapy was 69% in group R-CVP, compared with 32% in the CVP. Mabtera increases the time before the appointment of a new therapy or death, time to disease progression from 14.5 to 27 months (p <0.0001). After 12 months in 81% of patients treated with MabThera not observed recurrent disease, compared with 58% of patients receiving only the CVP. The advantages of a combination of MabThera with CVP were observed in all patients, regardless of age, number of extranodal lesions involving bone marrow, increasing the level of LDH, β2-microglobulin, the presence of B symptoms, bulky disease, number of affected sites, the hemoglobin values of the international prognostic index (IPI ) and index FLIPI in patients with follicular lymphoma.

Maintenance therapy

In patients with relapsed or resistant follicular non-Hodgkin's lymphoma therapy after induction therapy, R-CHOP or CHOP MabThera maintenance therapy significantly and statistically significantly increases progression-free survival to 42.2 months compared with 14.3 months in patients not receiving maintenance therapy reduces the risk of progression disease or death by 61%. The expected level of progression-free survival after 12 months in the group of maintenance therapy was 78% compared with 57% in the control group has not received MabThera maintenance therapy. Maintenance therapy with MabThera reduces the risk of death by 56%, increases the time before the appointment of new therapies (38.8 months compared to 20.1 months), and reduces the risk of the appointment of new therapies - up to 50%.

Patients with complete or unconfirmed complete response to the appointment of MabThera as maintenance therapy significantly improves survival without evidence of disease from 16.5 months to 53.7 months and reduces the risk of relapse by 67%. Benefits received MabThera maintenance therapy for all subgroups of patients regardless of the type of induction therapy (CHOP or R-CHOP), response to induction therapy (complete or partial response), and regardless of age, sex, stage of disease, the values of IPI, FLIPI, in -symptoms, involvement of bone marrow, the number of lymph nodes and extranodal foci, the number of previous modes of therapy, a better response to therapy, LDH, hemoglobin and β2-microglobulin, except for a subgroup of patients with bulky disease. Diffuse large non-Hodgkin's lymphoma

Application circuit R-CHOP (Mabtera 375 mg/m2 on the first day of the cycle in combination with CHOP: cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 up to a maximum of 1 mg on the first day of the cycle, and prednisolone 40 mg / m2/sut on days 1-5, every 3 weeks, with 8 cycles) in untreated patients in elderly (60 to 80 years) leads to a statistically significant increase "uneventful" survival from 13 to 35 months, compared with only scheme CHOP (p = 0.0001) (the "Events" refers deaths, relapses or progression of lymphoma, as well as the appointment of a new scheme of therapy).

Application of R-CHOP scheme reduces the risk of these events by 41%. The median duration of observation was 31 months. Overall survival in the group of R-CHOP was significantly increased to 68.2% compared with 57.4% in the CHOP group, with the risk of death decreased by 33% (p = 0.0094). Therapy scheme R-CHOP CHOP scheme also outperforms the frequency of complete remission by the end of treatment (76.2% and 62.4%, respectively, p = 0.0028). The risk of disease progression in the group of R-CHOP decreased by 46% and the risk of relapse - at 51%. The advantages of the scheme R-CHOP is not dependent on sex, age, IPI values, adjusted for age, ECOG, β2-microglobulin, LDH, albumin, B-symptoms, bulky disease, involvement in the bone marrow and extranodal lesions.

Rheumatoid arthritis

Rituximab in combination with methotrexate significantly reduces the activity of the disease. The clinical effect for at least 20% according to the criteria of the American College of Rheumatology (AKR20), compared with methotrexate monotherapy was observed in most patients, regardless of the titer of rheumatoid factor, age, sex, body surface area, race, previous therapy and disease activity. Clinically and statistically significant improvement in the treatment of MabThera noted with regard to all criteria, the AKP: the number of swollen and painful joints, pain index, C-reactive protein, rheumatoid factor, along with improving the overall evaluation of the effectiveness of treatment in the opinion of the physician and patient assessment of pain intensity according to patient index, degree of disability. Rituximab significantly reduces disease activity index DAS28. Good and moderate response by EULAR criteria was achieved in significantly more patients in the appointment of MabThera with methotrexate compared with methotrexate monotherapy.

Patients who received drug therapy Mabtera, noted a significant improvement in the index of disability (by questionnaire and health assessment - HAQ-DI), weakness (FACIT-F) and improving both physical and mental health indicators questionnaire SF-36. In the appointment of rituximab showed a significant decrease in the concentration of rheumatoid factor (range 45-64%). The concentration of immunoglobulins, the number of lymphocytes, white blood cells remained within normal limits, except for a transient reduction in the number of leukocytes in the first 4 weeks of therapy.

As with MabThera monotherapy and in combination with methotrexate showed a significant reduction in inflammatory markers (IL-6, CRH, serum amyloid protein type A protein isotype S100 A8 and A9). The frequency of response to therapy with MabThera re-treated patients is comparable to that in the first course of therapy.

Side effect

Reactions associated with infusion: fever, weakness, shortness of breath, indigestion, nausea, rash, flushing, hypotension, hypertension, fever, itching, rash, irritation of the throat, rhinitis, tachycardia, vomiting, pain, symptoms of tumor lysis syndrome.

In some cases, during the scheme R-CHOP: myocardial infarction, atrial fibrillation and pulmonary edema. Infections: upper respiratory tract infection (most often - nasopharyngitis, sinusitis, bronchitis, pneumonia, superinfection of the lungs), urinary tract infections, sepsis, herpes zoster, septic shock, infection of implants, staphylococcal septicemia; very rarely - reactivation of hepatitis B.
On the part of the hemopoietic system: leukopenia, neutropenia, thrombocytopenia, anemia, febrile neutropenia and less than 1% - lymphadenopathy, blood clotting, and very rarely - pancytopenia (4 weeks or more after the last administration of rituximab), a transient increase in the level of IgM in patients with makroglobulinemiey Valdenstrema, with subsequent return to its initial value after 4 months; partial transient aplastic anemia, hemolytic anemia.
On the part of the respiratory system: rhinitis, nasal mucus, bronchospasm, cough or increased cough, respiratory infection, dyspnea, acute respiratory failure, pulmonary infiltrates, less than 1% - hypoxia, pulmonary dysfunction, bronchiolitis obliterans, asthma.
On the part of the whole body: throat irritation, back pain, chest pain, pain in the neck, pain in the foci of the tumor, flu-like syndrome, peripheral edema, Mucosit, syncope, weight loss, multiple organ dysfunction syndrome, rapid lysis of the tumor; very rare - serum sickness and less than 1% - an increase in abdominal, anaphylactic reactions, pain at the injection site.
On the part of the digestive system: dyspepsia, nausea, vomiting, diarrhea, anorexia, dysphagia, stomatitis, constipation, abdominal pain.
Since the cardiovascular system: hypotension, hypertension, orthostatic hypotension, tachycardia, bradycardia, arrhythmia (including ventricular and supraventricular tachycardia, atrial fibrillation), unstable angina pectoris, vasodilatation, venous thrombosis, including extremity deep vein thrombosis, cardiac insufficiency, low ejection fraction, pulmonary edema, myocardial infarction, very rare: vasculitis, predominantly cutaneous (leukocytoclastic), ischemic cerebral circulation.
From the side of the central nervous system and peripheral nervous system: dizziness, headache, paresthesia, hypoesthesia, headache, confusion, and very rarely - neuropathy of cranial nerves, in conjunction with peripheral neuropathy with or without (marked reduction of visual acuity, hearing, failure of other organs emotions, facial nerve palsy) in different periods of therapy - until several months after treatment MabThera, confusion, less than 1% - anxiety, depression, anxiety, taste perversion.
From the Musculoskeletal System: myalgia, arthralgia, muscular hypertonicity, muscle cramps, osteoarthritis.
On the part of the endocrine system: hyperglycemia, diabetes decompensation. Dermatological reactions: itching, rash, urticaria, increased sweating at night, sweating, alopecia, very rarely - heavy bullous reaction, toxic epidermal necrolysis with fatal consequences.
From the senses: Violations watery, conjunctivitis, pain and tinnitus.
From the laboratory parameters: increase in activity of lactate dehydrogenase, hypocalcemia, hypercholesterolemia, hyperglycemia, bacteremia.

Monotherapy Infusion reactions often occur during the first infusion. The frequency of infusion reactions decreased from 77% (including 7% - 3, and 4 degrees) for 1 second infusion of up to 30% (2% - 3, and 4 degrees) at 4 and 14% (absence of reactions 3 and 4 degrees) at 8-second infusion.

Infections: Mabtera cause depletion of the pool of B cells in 70-80% of cases and reduce the concentration of immunoglobulins in serum in a small number of patients. 30.3% - infectious complications (for whatever reason), including 18.8% - bacterial infections, 10.4% - viral infections, 1.4% - fungal infections, 5.9% - infection without refined etiology (one patient could be different infection). Severe infections (3 and 4 degrees), including sepsis, were noted in 3.9% of patients: during therapy (1.4%) and in patients during observation without treatment (2.5%).
On the part of the hemopoietic system: severe thrombocytopenia (3 and 4 severity) was observed in 1.7% of patients, severe neutropenia - at 4.2% of patients with severe anemia and the severity (3, 4) - in 1.1% of patients. Have been reported 1 case of transient aplastic anemia and 2 cases of hemolytic anemia.
Since the cardiovascular system: side-effects were observed in 18.8% of cases, most often - arterial hypo-and hypertension.

Mabtera in combination with chemotherapy scheme SVP (R-CVP) Infusion reactions 3 and 4 degrees (9%): fever, weakness, shortness of breath, indigestion, nausea, rash, flushing. Infections: infections (33% during treatment and 28 days after the end of treatment, compared with 32% of patients who received only CVP), including upper respiratory tract infection (12.4%), most often - nasopharyngitis, serious infections (4.3%) life-threatening infections are not registered.
On the part of the blood system: neutropenia grade 3 and 4 severity (24%), neutropenia 4 degrees (3.1%). The higher incidence of neutropenia in the group of R-CVP does not increase the frequency of infections. Anemia - from 0.6% of patients in group R-CVP and in 1.9% of patients treated with CVP, thrombocytopenia - at 1.2% in group R-CVP and absent in patients treated with CVP. The overall incidence of cardiovascular disorders was similar in patients treated with CVP (5%) and R-CVP (4%).

Mabtera in combination with chemotherapy scheme CHOP (R-CHOP) Infusion reactions 3 and 4 degrees during the infusion or within 24 h after infusion of MabThera were observed during the first cycle of R-CHOP 9% of patients. By the eighth cycle of R-CHOP frequency of infusion reactions decreased to less than 1%. Infection: Infection 2-4 severity and / or febrile neutropenia in the group of R-CHOP - 55.4% in the CHOP group - 51.5%, febrile neutropenia without concomitant documented infection in patients receiving R-CHOP - 20.8% in patients receiving CHOP - 15.3%. The overall frequency of infections 2-4 degrees in the group R-CHOP was 45.5% in the CHOP group - 42.3%, with no marked difference in incidence of systemic bacterial and fungal infections.

The frequency of fungal infections 2-4 degrees in the group of R-CHOP was higher than in the CHOP group (4.5% and 2.6%, respectively), this difference was due to a higher rate of local candidiasis during therapy. The frequency of HSV infection 2-4 degrees, including with damage to the eye, was higher in group R-CHOP (4.5%) than in the CHOP group (1.5%), 7 of 9 cases recorded in group R-CHOP, the disease emerged during therapy.
On the part of the hemopoietic system: after each cycle, leukopenia (88% compared to 79%) and neutropenia (97% compared to 88%) 3 and 4 severity were observed more frequently in the R-CHOP group than in CHOP group, respectively.

Differences in the incidence of anemia 3 and 4 severity in the two groups was observed (19% in the CHOP group and 14% in the R-CHOP), there was no difference in the frequency of thrombocytopenia (15% in the CHOP group and 16% in the R-CHOP ). Time to resolution of all hematological disorders in two therapeutic groups were comparable.
Since the cardiovascular system: the frequency of cardiac arrhythmias 3 and 4 degrees, mostly supraventricular arrhythmias (tachycardia, atrial flutter and atrial fibrillation), a group of R-CHOP was higher (6.9%) than in the CHOP group (1.5%) .

All arrhythmias developed either in connection with the infusion of MabThera, or were associated with predisposing conditions, such as fever, infection, acute myocardial infarction, or concomitant diseases of the respiratory and cardiovascular systems. Group R-CHOP and CHOP did not differ among themselves on the frequency of other cardiac adverse events 3 and 4 degrees of severity, including heart disease, myocardial disease and manifestation of coronary heart disease.
From the side of the central nervous system and peripheral nervous system: during the first cycle of therapy in 4 patients (2%) of group R-CHOP with cardiovascular risk factors developed ischemic attacks due to thromboembolism, in contrast to 1.5% of patients in the CHOP group during observation without treatment. The difference between the groups in the incidence of other thromboembolic disorders was absent.

Rheumatoid arthritis

The frequency of infection is 0.9 cases per year, the proportion of heavy infections, some of which were fatal, was less than 0.05 cases per year. The frequency of malignant diseases after the appointment of MabThera was 1.5 per 100 patients per year and higher than in the population.

Specific categories of patients

The high tumor burden (the diameter of single foci of more than 10 cm): increased incidence of adverse reactions of grade 3-4 severity.

Elderly patients (over 65): the frequency and severity of side effects and side effects 3 and 4 severity did not differ from that in younger patients. Repeated therapy: frequency and severity of side effects did not differ from those in the initial therapy.

acute infectious diseases, expressed primary or secondary immunodeficiency;
Hypersensitivity to rituximab, a drug or any component of the mouse proteins.

Precautions to apply for respiratory failure in history, or tumor infiltration of the lungs, when the number of circulating malignant cells> 25 000/mkl or high tumor load (chronic lymphocytic leukemia, or lymphoma, mantle cell zone), neutropenia (less than 1500/mkl), thrombocytopenia (less than 75 000/mkl) for chronic infections.

Pregnancy and lactation

Effects of rituximab during pregnancy has not been studied. The injurious effect of MabThera in the fetus and the effect of the drug on fertility is unknown.

Given that the immunoglobulin class IgG penetrate through the placental barrier rituximab can cause depletion of the pool of B cells in the fetus. MabThera should not be given during pregnancy except in cases where the expected benefit of therapy to the mother outweighs the potential risk to the fetus. During the period of treatment and within 12 months after the end of women of childbearing age should use effective methods of contraception. It is not known whether rituximab is allocated through breast milk.

Given that the immunoglobulin class IgG, circulating in maternal blood, are provided with breast milk MabThera should not be used during lactation. Cautions MabThera introduced under the close supervision of oncologist, hematologist or rheumatologist, if the necessary conditions for resuscitation. The development of infusion reactions may be due to the release of cytokines or other mediators.

The majority of patients within 30 min-2 h after the first infusion of MabThera appear fever with chills or shivering. Severe reactions include symptoms from the lung, hypotension, urticaria, angioedema, nausea, vomiting, weakness, headache, itching, irritation of tongue or throat swelling (vascular edema), rhinitis, flushing, pain in the foci of the disease and, in some cases , signs of tumor lysis syndrome fast. Severe infusion reactions is difficult to distinguish from hypersensitivity reactions or cytokine release syndrome. There have been reports of fatal infusion reactions, described in the post-registration period of the drug.

Infusion reactions disappear after a delay or interruption of MabThera and the introduction of supportive measures (including on / in the introduction of 0.9% sodium chloride, diphenhydramine and acetaminophen, bronchodilators, SCS).

In most cases, after the complete disappearance of symptoms of infusion can be resumed at a rate of 50% from the previous (eg, 50 mg / h instead of 100 mg / h). The majority of patients with infusion reactions, no life-threatening, rituximab treatment was completed.

Adverse reactions in the lungs: may increase symptoms over time or clinical deterioration after initial improvement. Patients with pulmonary symptoms or other severe infusion reactions should be carefully observed until complete resolution of symptoms. Continuation of therapy after the complete disappearance of symptoms is rarely accompanied by a re-development of severe infusion reactions. Acute respiratory failure may be accompanied by the formation of interstitial infiltrates in the lungs or pulmonary edema, often seen in the first 1-2 h after the first infusion.

With the development of adverse reactions in the lungs infusion of rituximab should be stopped immediately and appoint an intensive symptomatic therapy. As an initial improvement of clinical symptoms can change as deterioration, patients should be carefully observed until the resolution of pulmonary symptoms. Rapid tumor lysis syndrome is possible after the first infusion of MabThera in patients with large numbers of circulating malignant lymphocytes.

Tumor lysis syndrome include hyperuricemia, hyperkalemia, hypocalcemia, acute renal failure, increased LDH. Patients at risk require careful medical supervision and conduct regular laboratory examination. With the rapid development of symptoms of tumor lysis conduct appropriate therapy. After complete relief of symptoms in a limited number of cases therapy.

MabThera continued in conjunction with the prevention of tumor lysis syndrome fast. Patients with large numbers of circulating malignant cells (more than 25 000/mkl) or high tumor burden (eg, chronic lymphocytic leukemia, or lymphoma cells from the mantle zone), in which the risk is extremely severe infusion reactions may be particularly high, MabThera should be prescribed with extreme caution , under the close supervision and only for inefficiency of all other methods of treatment. The first infusion of the drug in such patients should be administered at a lower speed.

Due to the potential development of anaphylactoid reactions during in / in the introduction of protein drugs must have a means for coping: epinephrine (adrenaline), antihistamines and corticosteroids.

During infusion requires careful monitoring of patients with cardiovascular disease history. Because of the possibility of hypotension is not less than 12 hours before the infusion of MabThera should be abolished antihypertensive drugs.

Although monotherapy with MabThera has no mielosupressivnogo actions need to be careful to make a decision on the appointment of the drug with less neutropenia and thrombocytopenia 1500/mkl least 75 000/mkl because the experience of its clinical application in such patients is limited. The use of MabThera in patients after autologous bone marrow transplantation and other high-risk groups with possible dysfunction of the bone marrow was not accompanied by symptoms of myelotoxicity.

In the course of treatment should be regularly conduct detailed analysis of the peripheral blood, including counting the number of platelets in accordance with routine practice. Infections: very rarely using the combination of MabThera to chemotherapy were observed reactivation of hepatitis B and fulminant hepatitis, whose connection with the reception MabThera is not installed.

Such patients should be carefully monitored. Immunization: The safety and effectiveness of immunization of any vaccine, particularly live viral vaccines, after treatment MabThera not been studied. Vaccination should be completed no less than 4 weeks prior to the appointment of rituximab. Vaccination with live vaccines is not recommended for reducing the number of B-cells.

Effects on ability to drive vehicles and management mechanisms

Does rituximab's ability to manage and work with machines and mechanisms is unknown, although pharmacological activity and the adverse effects described do not suggest such an influence.


Cases of overdose in humans have not been observed. Efficacy and safety of rituximab in single doses over 1 g were not studied.

Drug Interactions

Data on possible drug interactions are limited MabThera. In the appointment of other monoclonal antibodies for diagnostic or therapeutic purposes patients with antibodies against proteins of the mouse or antihimernye antibodies increases the risk of allergic reactions.

Tolerability of concurrent or sequential use of MabThera and drugs that can reduce the number of normal B-cells (in addition to the scheme CHOP or CVP), if not installed. Mabtera compatible with PVC and polyethylene infusion systems or packages.

Terms and Conditions of storage

The drug should be kept in the dark, away from children at a temperature of 2 ° to 8 ° C. Shelf life - 2.5 years.