Universal reference book for medicines
Product name: JAQUINUS

Active substance: tofacitinib

Type: Immunosuppressive drug

Composition, form of production and packaging
The tablets, coated with a
white film coating , are round, engraved with "Pfizer" on one side and "JKI 5" on the other;
the core of the tablet is white or almost white.
1 tab.

tofacitinib citrate 8.078 mg,

which corresponds to the content of tofacitinib 5 mg

Excipients: microcrystalline cellulose - 122.615 mg, lactose monohydrate - 61.307 mg, croscarmellose sodium - 6 mg, magnesium stearate - 2 mg.

The composition of the film shell: opadray 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).

14 pcs.
- blisters of aluminum foil (4) - packs of cardboard.

Description of the drug approved by the manufacturer for the printed edition of 2015.


Selective immunosuppressant.
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 Ianus kinases 1, 2, 3 and to a lesser extent tyrosine kinase-2. In those cells where the cannulas transmit the signal in pairs, tofacitinib preferably inhibits the transfer of the signal of heterodimeric receptors bound to janus kinase-3 and / or Janus kinase-1, having functional selectivity for receptors that transmit signals through pairs of Janus- kinase-2. Inhibition of Janus kinase-1 and Janus 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-α. At a higher exposure of the drug, inhibition of the transfer of the signal of Janus kinase-2 leads to inhibition of erythropoietin signaling.
Pharmacodynamic 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. The change in total serum levels of IgG, M and A over 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.

Suction and distribution

The profile of the pharmacokinetics of tofacitinib is characterized by rapid absorption (C max is achieved within 0.5-1 h), rapid elimination (T 1/2 for about 3 h) and a proportional dose increase in systemic exposure.
C ss is reached within 24-48 hours with a slight accumulation after taking 2 times / day.
Tofacitinib is well absorbed, its bioavailability is 74%.
The use of tofacitinib with food rich in fats was not accompanied by changes in AUC, while C max in blood plasma decreased by 32%. In clinical studies, tofacitinib was used regardless of food intake.
The binding of tofacitinib with plasma proteins is approximately 40%.
Tofacitinib predominantly binds to albumin and does not bind to? 1- acid glycoprotein.
It is equally distributed between erythrocytes and blood plasma.

Metabolism and excretion

The elimination of tofacitinib by approximately 70% is accomplished by metabolism in the liver and by 30% by kidney excretion in the form of unchanged tofacitinib.
The metabolism of tofacitinib is predominantly mediated by the isoenzyme CYP3A4 and, to a lesser extent, by the isoenzyme CYP2C19. In the study of radiolabeled tofacitinib, more than 65% of the total circulating radioactivity accounted for unchanged tofacitinib, and the remaining 35% - for 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 with a 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 AUC was less than 5% higher than in patients aged 55 years.

In women, the AUC of tofacitinib is 7% lower than that of men.

The data obtained also showed no significant differences (<5%) in the AUC of tofacitinib in patients of the Caucasoid, Negroid and Asian races.

An almost linear relationship between body weight and V d is observed , which leads to a higher C max and lower C min in plasma in patients with a lower body weight.However, this difference is not considered clinically significant.
Interindividual variability (% coefficient of variability) of AUC for tofacitinib is about 27%.
Pharmacokinetics in special clinical cases

In patients with mild, moderate or severe impairment of renal function, AUC were 37%, 43% and 123% higher, respectively, compared to healthy volunteers.
In patients with terminal stage of renal failure, the contribution of dialysis to the total clearance of tofacitinib is relatively small.
In patients with mild and moderate impairment of liver function, AUC values ​​were 3% and 65% higher than those of healthy volunteers.
Patients with severe impairment of liver function were not studied.
Studies of pharmacokinetics, safety and efficacy of tofacitinib in children have not been conducted.


- Moderate or severe active rheumatoid arthritis in adults with an inadequate response to one or more basic anti-inflammatory drugs (DMAP).


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 2 times / day.
Some patients may need to increase the dose to 10 mg 2 times / day, depending on the clinical response to therapy.
Correction of dose due to laboratory abnormalities

It may be necessary to adjust the dose or discontinue therapy in the event of development of dose-dependent deviations in laboratory indicators, including neutropenia and anemia (Tables 1 and 2).

It is not recommended to start therapy in patients with an absolute neutrophil count (AFN) of less than 1000 / μL and / or a hemoglobin level of less than 90 g / l.

Table 1. Correction of dose for neutropenia

Low level of ACN

Laboratory significance (cells / μL) Recommendations

АЧН> 1000 The dose remains at the same level.

АЧН 500-1000 At steady decrease in this range, it is necessary to lower a dose or to cancel reception.
With an increase in ACN of more than 1000 cells / μl, resumption of therapy in a dose of 5 mg 2 times / day is possible; In the future, depending on the clinical response, you can increase the dose to 10 mg 2 times / day.
АЧН <500 (confirmed with reassessment) Cancel therapy.

Table 2. Correction of the dose in anemia

Low level of hemoglobin

Laboratory value (g / l) Recommendations

90 and a decrease of less than 20 g / l The dose remains at the same level.
<80 or a decrease of 20 g / l or more (confirmed with a reassessment) The use of Yaquinus should be stopped before the hemoglobin level is normalized.

Special categories of patients

Patients with impaired renal function of mild to moderate severity do not need a dose adjustment.
In patients with severe renal dysfunction, the dose of Yaquinus should not exceed 5 mg 2 times / day.
Do not use Iaquinus in patients with severe liver dysfunction .
The dose of Yaquinus should not exceed 5 mg 2 times / day in patients with moderate impairment of liver function .
In elderly patients 65 years of age and older, dose adjustment is not required.

In patients receiving potent inhibitors of the isoenzyme CYP3A4, the dose of Yaquinus should not exceed 5 mg 2 times / day.

In patients receiving one or more concomitant drugs that can moderately inhibit the CYP3A4 isoenzyme and actively inhibit the CYP2C19 isoenzyme (eg, fluconazole), the dose of Yaquinus should not exceed 5 mg 2 times / day.

The simultaneous use of Yaquinus and powerful inhibitors of the CYP3A4 isoenzyme may lead to a reduction or loss of clinical efficacy.


The most frequent serious undesirable reactions, noted against the background of therapy with tofacitinib, 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 HDL) included upper respiratory tract infections, headache, nasopharyngitis, and diarrhea.

The withdrawal of therapy due to any adverse reaction during double-blind, placebo-controlled studies was required in 6.8% of cases for patients in the Yaquinus group and 3.7% 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.
Determination of the incidence of adverse reactions: very often (? 10%), often (? 1% and <10%), infrequently (? 0.1% and <1%), rarely (? 0.01% and <0.1% 0.01%), there is no information (it is impossible to determine based on available data).

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

Infections and parasitic infestations: very often - nasopharyngitis;
often - 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; rarely - tuberculosis of the central nervous system, 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 Mycobacterium avium complex, cytomegalovirus infection, bacteremia.
From the cardiovascular system: often - increased blood pressure.

On the part of the digestive system: often - abdominal pain, vomiting, gastritis, diarrhea, nausea, dyspepsia;
infrequently, steatosis of the liver.
From the side of metabolism: often - hyperlipidemia, dyslipidemia;
infrequently - dehydration.
From the nervous system: often - headache, insomnia;
infrequently paresthesia.
From the musculoskeletal system: often - pain in muscles and bones, arthralgia;
infrequently - tendonitis, swelling of the joints, muscle tension.
On the part of the hemostasis system: often - leukopenia, anemia;
infrequently - neutropenia.
On the part of the respiratory system: often - shortness of breath, cough;
infrequently, stagnation in the paranasal sinuses.
From the skin: often - a rash;
infrequently - erythema, itchy skin.
Benign, malignant and unspecified neoplasms (including cysts and polyps): infrequently skin cancer not associated with melanoma.

Laboratory and instrumental indicators: often - increased activity of liver enzymes, CK, increased concentrations of LDL, blood cholesterol (in clinical trials first observed after the first month of therapy and remained stable in the future), weight gain;
infrequently, an increase in the activity of transaminases, an increase in the concentration of creatinine in the blood plasma, an increase in the concentration of GGTP, a violation of functional liver samples.
Other: often - fever, fatigue, peripheral edema.


severe liver dysfunction;

- infection with hepatitis B and / or C viruses (presence of serological markers of HBV and HCV infection);

- SC less than 40 ml / min;

- simultaneous use of live vaccines;

- simultaneous use of Yaquinus with biological agents such as TNF inhibitors, interleukin antagonists (IL-1R, IL-6R), monoclonal anti-CD20 antibodies, selective co-stimulatory modulators, and potent immunosuppressants such as azathioprine, cyclosporine and tacrolimus, since this combination increases the likelihood of severe immunosuppression and the risk of infection;

- severe infections, active infections, including local infections;

- Pregnancy (safety and efficacy not studied);

- the period of breastfeeding;

- children and adolescents under 18 years of age (safety and efficacy not studied);

- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

- hypersensitivity to tofacitinib or to any other component of the drug.


- at an increased risk of perforation of the digestive tract (for example, in patients with a history of diverticulitis);

- in elderly patients due to a high risk of developing infectious diseases.


Adequate, well-controlled studies of the use of Yaquinus in pregnant women have not been conducted.

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.

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.

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.

Contraindicated for children under 18 years.


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


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 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 alone 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 studies (eg, histoplasmosis, coccidioidomycosis and listeriosis).
Yawrinus 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 a 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. Yaquinus should be temporarily discontinued if the patient develops a serious infection, an opportunistic infection or sepsis. 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 similar to a patient suffering from immunodeficiency. The appointment of appropriate antibiotic therapy as well as careful dynamic observation is shown.
Since elderly patients usually have a higher incidence of infection, caution is also necessary in such cases.


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 anti-tuberculosis therapy in each patient is advised to consult with a TB specialist.
Patients should be carefully monitored for signs of tuberculosis, including patients with a negative test for latent tuberculosis prior to initiating therapy.
The frequency of tuberculosis when used Yakvinus drug in the global clinical development program was 0.1-0.2%. Patients with latent tuberculosis before starting therapy with Yakvinus subject to standard antimycobacterial therapy.
Reactivation of viral infections
reactivation of viral infections described in the application DMARD therapy. Cases reactivation of herpes virus (e.g., herpes zoster) is also described in clinical studies Yakvinus preparation. Yakvinus influence of the drug on the reactivation of chronic HBV infection is unknown. Patients who test positive for hepatitis B and C are excluded from clinical trials. Before starting therapy with Yakvinus should be screened for the presence of viral hepatitis.
And malignant lymphoproliferative disease (except skin cancer, a non-melanoma)
There is a possibility that Yakvinus affects the body's defense against malignancies. Effect of drug therapy on the development and Yakvinus for malignant neoplasms is unknown, but cases of malignancies monitored in clinical trials of this drug.
Skin cancer is not related to melanoma (FCNM)
reported cases of the FCNM in patients receiving therapy tofacitinib. It is recommended to carry out a periodic examination of the skin 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 are described cases of perforation of the intestine, although the role of inhibition of Janus kinase in these events is not known. Such cases generally have been described as diverticulum perforation, peritonitis, abscess and appendicitis. All patients who developed perforation of the intestine, received concomitant NSAIDs and / or corticosteroids. The relative contribution of concomitant therapy, and the use of the drug in development Yakvinus perforation of the digestive tract is unknown.
Yakvinus should be used with caution in patients at increased risk of perforation of the digestive tract (eg, patients with a history of diverticulitis). Patients with new symptoms in the digestive tract are subject to immediate inspection for early detection of the perforation of the digestive tract.
Laboratory indicators

Neutrophils: treatment with Yakvinus accompanied by an increase in the incidence of neutropenia (<2000 / L) compared to placebo. Treatment with Yakvinus patients with low neutrophil concentration (ACHP less than 1000 / l) is not recommended. Patients with persistent reduction ANC to 500-1000 / ml should be reduced dose Yakvinus or discontinue treatment until ANC concentration of 1000 cells / .mu.l. Patients with an absolute neutrophil count below 500 / ml treatment is not recommended. neutrophil count should be monitored after 4-8 weeks of therapy and then every 3 months.
Hemoglobin is not recommended to start therapy with Yakvinus patients with low levels of hemoglobin (less than 90 g / l). Treatment with Yakvinus should stop in patients with Hb level less than 80 g / l, or with a decrease in hemoglobin level of 20 g / l or more during the treatment. Hemoglobin should be monitored at the initial stage of therapy, after 4-8 weeks of therapy and then every 3 months.
Lipids: treatment with Yakvinus accompanied by increased levels of blood lipids - total cholesterol, LDL cholesterol and HDL cholesterol. The maximal effect is usually observed for 6 weeks. Assessment of lipid parameters should be performed after about 4-8 weeks after initiation of therapy. The use of statins in patients with elevated concentrations of total cholesterol and LDL cholesterol by drug therapy Yakvinus achieves benchmarks.
Information on the response to vaccination or infection with secondary transmission live vaccines administered to patients receiving Yakvinus hitherto available. Do not enter live vaccines at the same time with the preparation Yakvinus. It is recommended that prior to the start of the drug Yakvinus all patients completed the required immunizations in accordance with current recommendations for vaccination.
Patients with impaired renal function

In clinical studies, the drug is not Yakvinus studied in patients with an initial clearance <40 mL / min.
Impact on the ability to drive vehicles and manage mechanisms

Studies of the effect Yakvinus drug on the ability to drive a car and work with the mechanisms have not been conducted.

Experience in the application of an overdose of the drug Yakvinus offline. Treatment - symptomatic and supportive. In case of overdose it is recommended to control the patient's condition for the development of signs and symptoms of adverse reactions. With the development of adverse reactions to assign appropriate therapy.There is no specific antidote.

Data on the pharmacokinetics in healthy volunteers who received single doses up to 100 mg, indicate that about 95% of the injected dose excreted within 24 hours.

The interaction affects the application of the drug Yakvinus
Since tofacitinib metabolized by the action of the isoenzyme CYP3A4, very likely interactions with drugs that inhibit or induce active isozyme. While the use of potent inhibitors isoenzyme CYP3A4 (e.g., ketoconazole), and while the use of one or more moderate inhibitors isoenzyme CYP3A4 isozyme and potent inhibitors of CYP2C19 (e.g., fluconazole) tofacitinib exposure increases. The simultaneous use of ketoconazole (a potent inhibitor of isozyme CYP3A4) and a single dose tofacitinib increases AUC and C maxtofacitinib 103% and 16% respectively. The simultaneous use of fluconazole (moderate inhibitor of isozyme CYP3A4, as well as a potent inhibitor of isozyme CYP2C19) increases the AUC and C max tofacitinib 79% and 27% respectively.
While the use of potent inducers isoenzyme CYP3A4 (eg, rifampicin) tofacitinib exposure decreases. The simultaneous use of rifampicin (a potent inducer of the isoenzyme CYP3A4) reduces the AUC and C max tofacitinib 84% and 74% respectively.
Probability CYP2C19 isozyme inhibitors influence or P-glycoprotein on the pharmacokinetics tofacitinib small.
The simultaneous use of tacrolimus (weak inhibitor of isozyme CYP3A4) tofacitinib AUC increases by 21% and reduces the Cmax tofacitinib 9%. The simultaneous use of cyclosporine (moderate inhibitor of isozyme CYP3A4) tofacitinib AUC increases by 73% and reduces C max tofacitinib 17%. Simultaneous use of multiple tofacitinib and powerful immunosuppressive drugs in patients with rheumatoid arthritis patients has not been studied.
Concomitant use with methotrexate (MTX 15-25 mg 1 time per week) did not affect the pharmacokinetics tofacitinib.
Interaction at which Yakvinus affect the pharmacokinetics of other drugs
Studies in vitro have shown that at concentrations tofacitinib even more than 150 times greater than C ss maxWhich is achieved when used in the recommended therapeutic dose, did not significantly inhibit or induce the activity of basic drugs metabolized isozymes CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. These results were confirmed by in vitro studies of drug interactions, which showed no change in the pharmacokinetics of midazolam, highly selective substrate isoenzyme CYP3A4, while the use of tofacitinib. These in vitro showed that the ability tofacitinib in therapeutic concentrations, inhibit transporters such as P-glycoprotein, organic anionic or cationic carriers is very low.
The simultaneous use of tofacitinib had no effect on the pharmacokinetics of oral contraceptives, levonorgestrel and etinilestradola in healthy women.
Simultaneous application tofacitinib with methotrexate at a dose of 15-25 mg 1 time / week. figures reduced AUC and C max of methotrexate to 10% and 13% respectively. These changes the pharmacokinetics of methotrexate did not require dose adjustments, or selection of individual doses of methotrexate.
In patients with rheumatoid arthritis tofacitinib clearance does not change with the passage of time. This indicates that tofacitinib no effect on the CYP isoenzymes activity in patients with rheumatoid arthritis. Thus, it is unlikely that the simultaneous use of substrates with CYP isoenzymes tofacitinib will result in a clinically significant increase in their metabolism in patients with rheumatoid arthritis.

The drug is released by prescription.


The drug should be stored out of reach of children at a temperature of no higher than 25 ° C.
Shelf life - 2 years.
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