Yaqurinus (Jakvinus)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceTofacitinibTofacitinib
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  • Yaqurinus
    pills inwards 
    Pfizer Manufakchuring Deutschland GmbH     Germany
    • Dosage form: & nbspFilm-coated tablets.
    Composition:

    1 tablet contains:

    active substance: Tofacitinib 5/10 mg in the form of tofacitinib citrate 8,078 / 16,155 mg. Excipients: cellulose microcrystalline 122,615 / 245,230 mg, lactose monohydrate 61,307 / 122,615 mg, croscarmellose sodium 6/12 mg, magnesium stearate 2/4 mg.

    film sheath: Drop off white 6 mg (hypromellose 2.4 mg, titanium dioxide 1.5 mg, lactose monohydrate 1.26 mg, macrogol 0.48 mg, triacetin 0.36 mg. Fade blue 12 mg (hypromellose 4.8 mg, titanium dioxide 2.724 mg, lactose monohydrate 2.52 mg, macrogol 0.96 mg, triacetin 0.24 mg, aluminum lacquer based on indigo carmine 0.24 mg, aluminum lacquer based on dye of brilliant blue 0.036 mg.

    Description:

    Dosage of 5 mg: white round tablets covered with a film sheath with engraving "Pfizer" on one side and "JKI 5 "- on the other.The core of the tablet is white or almost white.

    Dosage of 10 mg: blue round tablets covered with a film sheath with engraving "Pfizer" on one side and "JKI 10 "- on the other.

    On the cross-section, two layers are visible. The core of the tablet is white or almost white.

    Pharmacotherapeutic group:Selective immunosuppressants.
    ATX: & nbsp

    L.04.A.A.29   Tofacitinib

    Pharmacodynamics:

    Mechanism of action

    Tofacitinib is a potent, selective inhibitor of the Yanus kinase family, which has a high selectivity for other kinases of the human genome. According to the results of the study of kinases tofacitinib inhibits the Ianus kinases 1, 2, 3 and to a lesser extent - tyrosine kinase-2. In those cells where the Janus kinases transmit the signal in pairs, tofacitinib preferably inhibits the transmission of the signal of heterodimeric receptors bound to Ianus-kinase-3 and / or Janus kinase-1, having functional selectivity for receptors that transmit signals through the pairs of Janus kinase-2. Inhibition of Janus kinase-1 and Yamus-kinase-3 by tofacitinib inhibits signal transmission through common receptors containing gamma chains for several cytokines, including IL-2, -4, -7, -9, -15 and - 21. These cytokines perform an integrating role in the activation of lymphocytes, their proliferation, the functioning and inhibition of signal transmission, which leads to modulation of various aspects of the immune response. In addition, inhibition of Ianus kinase-1 results in impaired signal transmission under the action of additional pro-inflammatory cytokines, such as IL-6 and IFN-y.At a higher exposure of the drug, inhibition of the transfer of the signal of Janus kinase-2 leads to inhibition of erythropoietin signaling.

    Fermodynamic effects

    Treatment with Yaqurinus is accompanied by a dose-dependent decrease in circulating natural killers Cd16/56+. The estimated maximum reduction is achieved after about 8-10 weeks after the initiation of therapy. The described changes are usually resolved after 2-6 weeks after the end of therapy. Treatment with Yaqurinus was accompanied by a dose-dependent increase in the number of B cells. Changes in the number of circulating T-lymphocytes and their subpopulations were insignificant and unstable. The clinical significance of these changes is unknown. Change in total serum level IgG, M and A during the 6-month treatment period of patients with rheumatoid arthritis was small, dose independent and similar to that of placebo.

    After treatment with Yaquinus, patients with rheumatoid arthritis experienced a rapid decrease in serum C-reactive protein (C-RB), which persisted throughout the treatment period.Changes in the level of C-RB, noted in the treatment with Yaquinus, did not occur within 2 weeks after the discontinuation of therapy, which indicates a longer duration of pharmacodynamic activity compared with the half-life.

    Pharmacokinetics:

    The profile of the pharmacokinetics of tofacitinib is characterized by rapid absorption (maximum plasma concentration is reached within 0.5-1 hour), rapid elimination (half-life of about 3 hours) and a proportional dose increase in systemic exposure. The equilibrium concentration is reached within 24-48 hours with a slight accumulation after taking two times a day.

    Absorption and distribution

    Tofacitinib is well absorbed, and its bioavailability is 74%. The use of tofacitinib with food rich in fats was not accompanied by changes in the area under the concentration-time curve (AUC), whereas the maximum concentration (Cmax) in blood plasma is reduced by 32%. In clinical trials tofacitinib applied regardless of the meal.

    The binding of tofacitinib with plasma proteins is approximately 40%. Tofacitinib predominantly binds to albumin and does not bind to α 1-acid glycoprotein. Tofacitinib is equally distributed between red blood cells and blood plasma.

    Metabolism and excretion

    The clearance of tofacitinib by approximately 70% is achieved by metabolism in the liver and by 30% by excretion through the kidneys in the form of unchanged tofacitinib. Metabolism of tofacitinib is predominantly mediated by isoenzyme CYP3A4 and to a lesser extent isoenzyme CYP2C19. In the study of radiolabeled tofacitinib, more than 65% of the total circulating radioactivity accounted for unchanged tofacitinib, and the remaining 35% - 8 metabolites (each - less than 8% of total radioactivity). Pharmacological activity is associated with nonmetabolized tofacitinib.

    Pharmacokinetics in patients with rheumatoid arthritis

    It was found that in patients with rheumatoid arthritis AUC Tofacitinib at the minimum and maximum body weight (40 and 140 kg) were similar to those in patients weighing 70 kg.

    In elderly patients at the age of 80 years, the indicator AUC was less than 5% higher compared with patients aged 55 years.

    Among women AUC Tofacitinib is 7% lower in comparison with men. The data obtained also showed no significant differences (<5%) AUC tofacitinib in patients of the Caucasian, Negroid and Asian races. An almost linear relationship between the body mass and the volume of distribution is noted, which leads to the achievement of a higher Cmax and a lower minimum concentration (Cmax) in blood plasma in patients with a lower body weight. However, this difference is not considered clinically significant. Interindividual variability (% coefficient of variability) of the indicator AUC for tofacitinib is about 27%.

    Impaired renal function

    In patients with mild, moderate or severe impairment of renal function AUC were higher by 37%, 43% and 123%, respectively, compared with healthy volunteers. In patients with terminal stage of renal failure, the contribution of dialysis to the total clearance of tofacitinib is relatively small.

    Impaired liver function

    In patients with mild and moderate impairment of liver function AUC by 3%

    and 65% more than in healthy volunteers.

    Patients with severe liver dysfunction or patients with positive

    serological tests HBV or HCV not studied.

    Childhood

    Studies of pharmacokinetics, safety and efficacy of tofacitinib in children have not been conducted.

    Indications:Yaquius is indicated for the treatment of adult patients with moderate or severe active rheumatoid arthritis with an inadequate response to one or more basic anti-inflammatory drugs (DMAP).
    Contraindications:
    - hypersensitivity to tofacitinib or to any other component of the drug;
    - severe liver dysfunction;
    - infection with hepatitis B and / or C viruses (presence of serological markers of HBV and HCV infection);
    - creatinine clearance less than 40 ml / min;
    - simultaneous use of live vaccines;
    - simultaneous use of Yaquinus with biological preparations, such as tumor necrosis factor inhibitors (FIO), interleukin antagonists (IL-IR, IL-6R), monoclonal anti-CD20 antibodies, selective co-stimulating modulators, as well as potent immunosuppressants, such as azathioprine, ciclosporin and tacrolimus, since this combination increases the likelihood of severe immunosuppression and the risk of infection;
    - severe infections, active infections, including local, severe infectious diseases;
    - deficiency of lactase, lactose intolerance, glucose-galactose malabsorption;
    - pregnancy (safety and efficacy not studied);
    - the period of breastfeeding;
    - children under 18 years of age (safety and efficacy not studied).
    Carefully:
    Yaqurinus should be used with caution:
    - at increased risk of perforation of the gastrointestinal tract (GIT) (for example, in patients with a history of diverticulitis).
    - in the elderly due to a high risk of developing infectious diseases.
    Pregnancy and lactation:
    Adequate, well-controlled studies of the use of Yaquinus in pregnant women have not been conducted. Yawrinus should not be taken during pregnancy.
    The ability of tofacitinib to penetrate breast milk in humans has not been studied. It is necessary to stop breastfeeding during the period of therapy with Yaquinus.
    Dosing and Administration:

    Inside, regardless of food intake.

    Yaquinus can be used as a monotherapy or in combination with methotrexate or other non-biological DMARD.

    The recommended dose is 5 mg twice daily. Some patients may need to increase the dose to 10 mg twice daily, depending on the clinical response to therapy.

    Correction of dose due to laboratory abnormalities

    Dose adjustment or discontinuation of therapy may be required if dose-dependent laboratory abnormalities develop, including lymphopenia, neutropenia, and anemia (see Tables 1, 2 and 3).

    It is not recommended to start therapy in patients with an absolute neutrophil count (ACH) less than 1000 / mm3 and / or with a hemoglobin level of less than 9 g / dl. It is not recommended to start therapy with the drug in patients with a lymphocyte count of less than 500 cells / mm3.

    Table 1. Dose Correction for Lymphopenia

    Reduced number of leukocytes

    Analysis result (cells / mm3)

    Recommendations

    The number of lymphocytes is greater than or equal to 500

    Without changes

    The number of lymphocytes is less than 500 (confirmed by repeated analysis)

    Discontinuation of treatment

    Table 2. Correction of dose for neutropenia

    Low level of ACN

    Laboratory significance (cells / mm)3)

    Recommendations

    АЧН> 1000

    The dose remains at the same level.

    АЧН 500-1000

    With a steady decrease in this range, you should lower the dose or cancel the intake until reaching ACHN more than 1000 cells / mm3.

    With an increase in ACN more than 1000 cells / mm3, it is possible to resume therapy at a dose of 5 mg twice a day; In the future, depending on the clinical response, you can increase the dose to 10 mg twice a day.

    LCHN <500 (confirmed with a second assessment)

    Cancel therapy.

    Table 3. Correction of the dose in anemia

    Low level of hemoglobin

    Laboratory significance (g / dL)

    Recommendations

    > 9.0 g / dl and a decrease of 2 g / dl or less

    The dose remains at the same level.

    <8.0 g / dL, or a decrease of more than 2 g / dL (confirmed by reassessment)

    You should stop using Yaquinus before normalizing hemoglobin.

    Special categories of patients

    Impaired renal function

    Patients with impaired renal function of mild to moderate severity do not need a dose adjustment.

    The dose of Yaquinus should not exceed 5 mg twice daily in patients with severe renal dysfunction.

    Impaired liver function

    In patients with impaired liver function of mild severity, dose adjustment is not required. Do not use Iaquinus in patients with severe liver dysfunction.The dose of Yaquinus should not exceed 5 mg twice daily in patients with moderate impairment of liver function.

    Simultaneous use with cytochrome P450 inhibitors (CYP3A4) and isoenzyme CYP2C19

    In patients receiving potent inhibitors of isoenzyme CYP3A4 (eg, ketoconazole), the dose of Yaquinus should not exceed 5 mg twice a day. In patients receiving one or more concomitant drugs capable of moderately inhibiting the isoenzyme CYP3A4 and actively inhibit isoenzyme CYP2C19 (eg, fluconazole), the dose of Yaquinus should not exceed 5 mg twice a day.

    Simultaneous application of the Yaquinus preparation and powerful isoenzyme inducers CYP3A4 (eg, rifampicin) may lead to a reduction or loss of clinical effectiveness (see section "Interaction with other drugs").

    Elderly patients (> 65 years)

    Correction of dose in patients aged 65 years and older is not required.

    Side effects:
    The most frequent serious undesirable reactions noted on the background of tofacitinib therapy were serious infections.
    The most frequent adverse reactions during the first 3 months of controlled clinical trials (with development in more than 2% of patients,who received monotherapy with Yaquinus or a combination with DMARD), included upper respiratory tract infections, headache, nasopharyngitis, and diarrhea. The abolition of therapy during the first 3 months due to any adverse reaction during double-blind, placebo-controlled studies was required in 4.2% of cases for patients in the Yaquinus group and 3.2% for patients in the placebo group. The most frequent adverse reactions that led to the withdrawal of Yaquinus were infections. The most frequent infections leading to cancellation of therapy included herpes zoster and pneumonia. The frequency of unwanted reactions is represented by the following classification:
    Very Frequent >10 %
    Frequent >1% and <10%
    Infrequent >0.1% and <1%
    Rare > 0.01% and <0.1%
    Very rare <0.01%
    No information can not be determined from the available data

    In each frequency group, adverse reactions are presented in order of severity.

    Infectious u parasitic diseases: very frequent - Nasopharyngitis; frequent - pneumonia, herpes zoster, bronchitis, influenza, sinusitis, urinary tract infections, pharyngitis; infrequent - sepsis, bacterial pneumonia, pneumococcal pneumonia, pyelonephritis, inflammation of subcutaneous fat, viral gastroenteritis, viral infection, herpes simplex; rare - tuberculosis of the central nervous system (CNS), encephalitis, necrotizing fasciitis, cryptococcal meningitis, disseminated tuberculosis, urosepsis, pneumonia caused by Pneumocystis jiroveci, Staphylococcal bacteremia, tuberculosis, bacterial arthritis, atypical infection caused by mycobacteria, infection caused by the complex Mycobacterium avium, cytomegalovirus infection, bacteremia. Among patients who took Yaquinus, the incidence of serious infections was higher in people older than 65 years than in persons younger than 65 years.

    From the cardiovascular system: frequent - increase in blood pressure.

    From the digestive system: frequent - pain in the abdomen, vomiting, gastritis, diarrhea, nausea, dyspepsia.

    From the side of metabolism: frequent - hyperlipidemia, dyslipidemia; infrequent - dehydration.

    From the nervous system: frequent - headache; infrequent - paresthesia. Mental disorders: frequent - insomnia.

    From the musculoskeletal system and connective tissue: frequent - pain in muscles and bones, arthralgia; infrequent - teidipit, swelling of the joints, muscle tension.

    From the side of the blood and lymphatic system: frequent - Lakopenia, anemia; infrequent - Neutropenia, lymphopenia.

    Confirmed cases of a decrease in the number of lymphocytes to less than 500 cells / mm3 accompanied by an increase in the incidence of treatment and serious infections. There was no clear correlation between neutropenia and the occurrence of serious infections.

    From the respiratory system: frequent - shortness of breath, cough; infrequent - congestion in the paranasal sinuses.

    From the skin: frequent - rash; infrequent - erythema, itchy skin. From the liver and bile ducts: infrequent - fatty hepatosis. Benign, malignant and unspecified neoplasms (including cysts and polyps): infrequent Skin cancer that is not associated with melanoma.

    Violations revealed in clinical and laboratory studies: frequent - increased activity of liver enzymes, creatine phosphokinase (CKF), increased concentration of low-density lipoprotein (LDL), blood cholesterol (in clinical trials first observed after the first month of therapy and remained stable in the future), weight gain; infrequent - increased transaminase activity, increased creatinine concentration in the blood plasma, increased concentrations of gamma-glutamyl transferase (GGT), impaired functional liver tests. With an increase in the activity of hepatic enzymes, a decrease in the dose of concomitant BPVP, the cancellation or reduction of the dose of Yaquinus resulted in a decrease or normalization of this parameter.

    Common disorders and reactions at the site of administration: frequent - fever, fatigue, peripheral edema.

    Trauma, intoxication and complications of manipulation: frequent - sprain; infrequent - Crick.

    Overdose:
    The experience of an overdose with the use of Yaquinus is absent. Treatment is symptomatic and supportive. In case of an overdose, it is recommended that the patient be monitored for signs and symptoms of unwanted reactions. If unwanted reactions develop, appropriate therapy should be prescribed. There is no specific antidote.
    Data on pharmacokinetics in healthy volunteers who received single doses up to 100 mg indicate that about 95% of the administered dose is excreted within 24 hours.
    Interaction:

    Interactions that affect the use of Yaqurinus

    Because the tofacitinib metabolized by isoenzyme CYP3A4, it is very likely that interaction with drugs that inhibit or induce this isoenzyme. When used simultaneously with potent inhibitors of isoenzyme CYP3A4 (eg, ketoconazole), as well as with simultaneous use with one or more moderate isoenzyme inhibitors CYP3A4 and potent inhibitors of isoenzyme CYP2C19 (eg, fluconazole), the exposure to tofacitinib increases (see the section "Dosing and Administration"). Simultaneous use of ketoconazole (a potent inhibitor of isoenzyme CYP3A4) and a single dose of tofacitinib raises AUC and CmOh tofacitinib by 103% and 16%, respectively. Simultaneous application of fluconazole (a moderate inhibitor of isoenzyme CYP3A4, as well as a potent inhibitor of isoenzyme CYP2C19) increases the AUC and CmOh tofacitinib by 79% and 27%, respectively.

    When used simultaneously with powerful isoenzyme inducers CYP3A4 (eg, rifampicin), exposure to tofacitinib decreases. The simultaneous use of rifamnicin (a powerful isoenzyme inducer CYP3A4) reduces AUC and CmOh tofacitinib by 84% and 74%, respectively (see Fig.See section "Dosing and Administration").

    The probability of the effect of inhibitors of the isoenzyme CYP2C19 or P-glycoprotein on the pharmacokinetics of tofacitinib is small.

    The simultaneous use of tacrolimus (a weak isoenzyme inhibitor CYP3A4) increases the AUC tofacitinib by 21% and reduces Cmax tofacitinib by 9%. Simultaneous use of cyclosporine (a moderate inhibitor of isoenzyme CYP3A4) increases the AUC tofacitinib by 73% and reduces CmOh tofacitinib by 17%. Simultaneous multiple application of tofacitinib and potent immunosuppressants in patients with rheumatoid arthritis was not studied.

    Simultaneous use with methotrexate (15-25 mg methotrekeate once a week) does not affect the pharmacokinetics of tofacitinib.

    Interactions in which Yaquinus affects the pharmacokinetics of other drugs Research in vitro showed that tofacitinib in concentrations that are even more than 150 times higher than the equilibrium CmOh, which occurs when the recommended therapeutic dosages are used, does not substantially inhibit or induce the activity of the main drugs metabolized by cytochromes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4). These results were confirmed by studies in vitro drug interaction, which showed no changes in the pharmacokinetics of midazolam, a highly selective substrate of isoenzyme CYP3A4, with simultaneous use with tofacitinib. Data in vitro showed that the ability of tofacitinib at therapeutic concentrations to inhibit carriers such as P-glycoprotein, organic anionic or cationic carriers is very low.

    Simultaneous use with tofacityib did not affect the pharmacokinetics of oral contraceptives, levonorgestrel and ethinylestradol in healthy women. The simultaneous use of tofacitinib with methotrexate at a dose of 15-25 mg once a week reduced the indices AUC and CmOh methotrexate by 10% and 13%, respectively. These changes in the pharmacokinetics of methotrekeat did not require dose adjustment, or the selection of individual doses of methotrekeate.

    In patients with rheumatoid arthritis, the clearance of tofacitinib did not change over time. This shows that. what tofacitinib does not affect the activity of SRS isoenzymes in patients with rheumatoid arthritis.Thus, it is unlikely that the simultaneous use of substrates of SRS isoenzymes with tofacitinib leads to a clinically significant increase in their metabolism in patients with rheumatoid arthritis. The concomitant administration of Yaquinus did not affect the pharmacokinetics of metformin, indicating that tofacitinib does not affect the carrier of organic cations (OCT2) in healthy volunteers.

    Special instructions:

    Serious infections

    In patients with rheumatoid arthritis receiving immunomodulators, including biological agents and Yaquinus, serious and sometimes fatal infections are noted, caused by bacterial, mycobacterial, fungal, viral or other opportunistic pathogens. The most frequent serious infections noted with the use of the drug Yaquinus include pneumonia, inflammation of the subcutaneous tissue, herpes zoster and urinary tract infection. Among the opportunistic infections with the use of Yaquinus, cases of development of tuberculosis and other mycobacterial infections, cryptococcosis, esophageal candidiasis, shingles with lesions of various dermatomes, cytomegalovirus infection, and VC-viral infection were noted.Some patients noted disseminated, diseases, most often with the simultaneous use of immunomodulators - methotrexate or corticosteroids. which themselves and in addition to the underlying disease of rheumatoid arthritis can predispose to the development of infections. It is also possible to develop other serious infections that have not been documented in clinical trials (eg, histoplasmosis, coccidiomycosis and listeriosis).

    Yawquius should not be used in patients with active infection, including local infections. Before applying Yaquinus, the risk / benefit ratio of patients with a chronic or recurrent infection should be assessed, after contact with a tuberculosis patient with a history of severe or opportunistic infection, in patients who have lived or recently visited endemic areas for tuberculosis or mycoses, and in patients with a predisposition to developing infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after therapy with Yaquinus.Yakvinus be temporarily canceled when the patient developed a serious infection, opportunistic infection, or sepsis, as long as there is no established control over the condition of the patient. With the development of a new infection, with the use of the Yaquinus preparation, the patient is subject to a rapid and complete diagnostic examination but analogy with a patient suffering from immunodeficiency. The appointment of appropriate antibiotic therapy as well as careful dynamic observation is shown.

    Because elderly patients are usually characterized by a higher rate of development

    infections, in such cases, too, should be careful.

    Tuberculosis

    Before using Yaquinus, a check should be made for signs of latent or active tuberculosis infection.

    Before starting therapy with Yakvinus in patients with latent or active tuberculosis in history, in the absence of confirmation of adequate TB treatment, as well as in patients with a negative result of a study on latent tuberculosis, but the presence of risk factors for tuberculosis infection should undergo proper TB treatment.When deciding on the need for antituberculous therapy, it is recommended that in each individual patient, a consultation with the TB specialist is recommended.

    Patients should be closely monitored for signs of tuberculosis, including patients with negative latency tuberculosis before initiating therapy.

    The incidence of tuberculosis in the application of Yaquinus in the world clinical development program was 0.1-0.2%. Patients with latent tuberculosis should be treated with standard antimycobacterial therapy before starting therapy with Yaquinus.

    Reactivation of viral infections

    Reactivation of viral infections is described in the application of therapy with BPD. Cases of reactivation of the herpes virus (eg, herpes zoster) are also described in clinical studies of the drug Yaquiius. The effect of Yaquinus on the reactivation of chronic viral hepatitis is unknown. Patients with a positive test result for hepatitis B and C were excluded from clinical trials. Before starting therapy with Yaquinus, screening for the presence of viral hepatitis should be performed.

    Malignant and lymphoproliferative diseases (with the exception of skin cancer, not related to melanoma (FCNM))

    There is a possibility that Yaquinus affects the protection of the body from malignant neoplasms. The effect of Yakvinus therapy on the development and course of malignant neoplasms is unknown, however, in clinical trials of this drug, cases of development of malignant neoplasms were recorded. The patients treated with Yaquinus received cases of lymphoma. Despite the fact that patients with rheumatoid arthritis, especially with a highly active form of the disease, have a higher risk (several times higher) of lymphoma than the general population, the role of inhibition of Janus kinases (JAK), if any, is unknown in the development of lymphoma.

    Skin cancer not related to melanoma (FCNM)

    Cases of development of FCNM in patients receiving therapy with tofacitinib have been reported. It is recommended to conduct periodic skin examination in patients with an increased risk of developing skin cancer.

    Cases of perforation of the digestive tract

    In clinical studies of patients with rheumatoid arthritis, cases of perforation of the gastrointestinal tract have been described, although the role of inhibition of the Yanus kinase is unknown in these phenomena. Such cases were mainly described as perforation of the diverticulum, peritonitis, abscess in the abdominal cavity and appendicitis. All patients who developed perforation of the gastrointestinal tract received concomitant therapy with non-steroidal anti-inflammatory drugs (NSAIDs) and / or glucocorticoids. The relative contribution of concomitant therapy and the use of the drug Yaquinus in the development of perforation of the gastrointestinal tract is unknown.

    Yaquinus should be used with caution in patients with an increased risk of perforation of the gastrointestinal tract (for example, in patients with a history of diverticulitis). Patients with new symptoms from the gastrointestinal tract are subject to immediate examination for early detection of perforation of the digestive tract.

    Laboratory indicators

    Lymphocytes: cases of a decrease in the number of lymphocytes to less than 500 cells / mm "were associated with an increase in the frequency of serious infections that required therapy." It is not recommended to initiate therapy with Yaquinus in patients with a low number of lymphocytes (ie, less than 500 cells / mm3).If the patient is confirmed to reduce the absolute number of lymphocytes to less than 500 cells / mm3, drug treatment

    Yaqurinus is not recommended. The level of lymphocytes must be monitored at the baseline and then every 3 months (see the "Method of administration and dose" section).

    Neutrophils: treatment with Yaquinus was accompanied by an increase in the frequency of neutropenia (<2000 cells / mm3) compared with placebo. Treatment with Yaquinus for patients with a low concentration of neutrophils (AChN less than 1000 cells / mm3) Not recommended. In patients with a persistent decrease in ACN up to 500-1000 cells / mm3 It should be reduced the dose of Yaquinus or discontinued treatment to achieve an ACN concentration of more than 1000 cells / mm3. In patients with a confirmed absolute neutrophil count of less than 500 cells / mm3 treatment is not recommended. The level of neutrophils should be monitored at the baseline and after 4-8 weeks of therapy, and then every 3 months (see the sections "Dosing and Administration", "Side effect").

    Hemoglobin: It is not recommended to begin therapy with Yaquinus in patients with low hemoglobin levels (less than 9 g / dl). Treatment with Yaquinus should be discontinued in patients with a hemoglobin level of less than 8 g / dL, or with a decrease in hemoglobin level of 2 g / dL or more on the background of treatment.Hemoglobin should be monitored at the initial stage of therapy, after 4-8 weeks of therapy, and then every 3 months (see the "Application and dosage" section)

    Lipids: treatment with Yakvinus is accompanied by an increase in blood lipids - total cholesterol, LDL cholesterol, and high-density lipoprotein cholesterol (HDL). The maximum effect was usually observed within 6 weeks. Evaluation of lipid parameters should be performed after about 4-8 weeks after initiation of therapy. The use of statins in patients with an increased concentration of total cholesterol and LDL cholesterol against the background of therapy with Yakivius allows to achieve baseline values.

    Vaccinations

    Information on the response to vaccination or secondary transmission of infection when administering live vaccines to patients receiving Yaquinus has not been reported to date. It is not recommended to administer live vaccines at the same time as Yaquinus. It is recommended that before the application of the Yaquinus preparation all patients perform the necessary immunization in accordance with modern vaccination recommendations.

    Patients with impaired function of night

    In clinical trials, Yaquiius was not studied in patients with baseline creatinine clearance less than 40 mL / min (calculated using the Cockcroft-Gault formula) (see "Contraindications").

    Effect on the ability to drive transp. cf. and fur:Studies of the effect of Yaquinus on the ability to drive and work with mechanisms have not been carried out.
    Form release / dosage:
    Tablets film-coated 5 mg and 10 mg.

    Packaging:
    For 14 tablets in a blister of aluminum foil.
    4 blisters together with instructions for use in a cardboard bundle.
    Storage conditions:Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
    Shelf life:
    2 years.
    Do not use the product after the expiry date printed on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:LP-002026
    Date of registration:16.03.2013
    The owner of the registration certificate:Pfizer Manufakchuring Deutschland GmbH Pfizer Manufakchuring Deutschland GmbH Germany
    Manufacturer: & nbsp
    Representation: & nbspPfizer H. Si. Pi. CorporationPfizer H. Si. Pi. Corporation
    Information update date: & nbsp12.09.2015
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