Tysabri

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Tizabri: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Tizabri

ATX code: L04AA23

Active ingredient: natalizumab (natalizumab)

Manufacturer: Vetter Pharma-Fertigung, GmbH & Co. KG (Germany)

Description and photo updated: 2018-16-08

Concentrate for the preparation of solution for infusion TYSABRI

Tysabri is a medical immunobiological drug (MIBP) with immunosuppressive action, used in multiple sclerosis.

Release form and composition

Dosage form - a concentrate for the preparation of a solution for infusion: colorless, transparent or slightly opalescent liquid (15 ml each in glass vials, 1 vial in a cardboard box and instructions for use of TYSABRI).

Composition of 1 ml of concentrate:

active ingredient: natalizumab - 20 mg;
auxiliary ingredients: sodium dihydrogen phosphate monohydrate, sodium hydrogen phosphate heptahydrate, sodium chloride, polysorbate 80, water for injection.

Pharmacological properties

Pharmacodynamics

Natalizumab is an active substance in TYSABRI that selectively inhibits adhesion molecules, binds to the α4-subunit of human integrin, which is expressed in large quantities on the surface of all types of leukocytes, except for neutrophils. The substance specifically binds to α4β1-integrin, while blocking the interaction with the corresponding receptor, the vascular cell adhesive molecule (VCAM-1) and the osteopontin ligand, the fibronectin domain formed as a result of alternative splicing, the connecting segment-1 (CS-1). Natalizumab also blocks the interaction of α4β7 integrin with the mucosal adhesion molecule, addressin-1 (MadCAM-1). The influence of the substance at the molecular level on these reciprocal reactions prevents the spread of mononuclear leukocytes through the endothelium into the inflammatory foci of parenchymal organs. The further mechanism of action of natalizumab is possibly due to the inhibition of inflammatory processes in the affected tissues by inhibiting the interaction of α4-expressing leukocytes with their ligands in the extracellular substance and on parenchyma cells. Tysabri is able to suppress inflammatory activity in the affected tissues and further reduce the attraction of immune cells to the focus of inflammation.

A consequence of MS (multiple sclerosis) is damage to the brain tissue that occurs when activated T-lymphocytes cross the BBB (blood-brain barrier). As a result of the migration of leukocytes through the BBB, adhesion molecules on the surface of activated leukocytes interact with the endothelium of blood vessels. The relationship between α4β1-integrin and its targets is an important component of the pathogenesis of the formation of inflammatory foci in the brain. Due to the violation of these connections, the activity of inflammation decreases. In the normal state, VCAM-1 is not expressed in the brain parenchyma. However, proinflammatory cytokines activate the production of VCAM-1 in endothelial cells and, possibly, in glial cells located near the focus of inflammation, which corrects according to the PIC principle (positive feedback). In the conditions of inflammatory diseases of the central nervous system (central nervous system) of patients with PC α4β1, when interacting with osteopontin, VCAM-1 and CS-1 mediates strong adhesion and migration of leukocytes in the brain, and can also enhance the inflammatory cascade in the tissues of the central nervous system. Blockade of molecular interactions between α4β1 and its targets in patients with MS decreases the inflammatory activity in the brain parenchyma and suppresses the further attraction of immune cells to inflammation foci. This reduces the formation or inhibits the growth of the lesion volume in MS. Blockade of molecular interactions between α4β1 and its targets in MS patients decreases the inflammatory activity in the brain parenchyma and suppresses the further attraction of immune cells to inflammation foci. This reduces the formation or inhibits the growth of the lesion volume in MS. Blockade of molecular interactions between α4β1 and its targets in MS patients decreases the inflammatory activity in the brain parenchyma and suppresses the further attraction of immune cells to inflammation foci. This reduces the formation or inhibits the growth of the lesion volume in MS.

Preclinical Safety Study Results:

multiple preclinical studies: no specific factors of genotoxicity and risk to human health have been identified;
in vivo studies: in most cases, there was a change in the migration of lymphocytes, which corresponds to the pharmacological activity of natalizumab; an increase in the number of leukocytes and an increase in the mass of the spleen were recorded. The changes were reversible and did not cause visible toxicological consequences;
experiments on mice: due to the introduction of natalizumab, there was no acceleration of melanoma cell division, as well as lymphoblastic leukemia;
study by the Ames method or analysis for chromosomal aberrations: no mutagenic effect was detected when using natalizumab in humans;
in vitro study of the proliferation of tumor cell lines containing α4-integrin: no signs of cytotoxicity were found;
experiments on guinea pigs: when using doses higher than recommended for humans, the effect of natalizumab on the reproductive ability of males was not observed, but in one study, a decrease in fertility was noted in females.

Evaluation of the effect of TYSABRI on reproductive function was carried out based on the results of five studies, of which three on guinea pigs, and two on Cynomolgus monkeys. These studies did not show teratogenicity or the effect of the drug on offspring growth. In one of the experiments on guinea pigs, there was a slight decrease in the survival rate of pups. In the group of monkeys who received 30 mg / kg of natalizumab, the frequency of spontaneous abortions increased by a factor of two compared with the control group. Another study found no effect on spontaneous abortion rates. A study of pregnant female Cynomolgus monkeys showed effects of natalizumab on the fetus, including a decrease in platelet counts, complete anemia, a decrease in liver and thymus mass, and an increase in spleen mass. Such changes were caused by an increase in extramedullary hematopoiesis in the spleen,atrophy of the thymus and inhibition of hematopoiesis in the liver. A decrease in platelet count was also noted in the offspring of females who received natalizumab before delivery, but no signs of anemia were observed in the pups. All pathologies were recorded at doses exceeding those recommended for humans and returned to normal after the cessation of therapy.

In some of the female Cynomolgus monkeys who received natalizumab before giving birth, a small amount of it was detected in milk, which indicates the possibility of natalizumab release during lactation in women.

Pharmacokinetics

In patients with MS, as a result of repeated intravenous (iv) administration of natalizumab at a dose of 300 mg, its C _max (average maximum serum concentration) was 110 ± 52 μg / ml, C _ss (average stationary concentration) of the substance during the administration period was 23– 29 μg / ml, T _Css (predicted time to reach equilibrium concentration) - approximately 36 weeks.

The pharmacokinetic analysis used the results of observations of more than 1100 MS patients who received natalizumab at a dose of 3–6 mg / kg (581 of them received a fixed dose of 300 mg of natalizumab as monotherapy). The mean ± SD (standard deviation) of the clearance time at steady state is 13.1 ± 5 ml / h, the mean ± SD elimination half-life is 16 ± 4 days. The analysis took into account the effect on pharmacokinetics of selected variables, including gender, age, body weight, liver / kidney function, and the presence of antibodies to natalizumab. It was found that the distribution of the drug is influenced only by the patient's body weight and the presence of antibodies to natalizumab. It was revealed that the effect of body weight on the clearance of natalizumab is less proportional, for example, at 43% body weight change, the clearance changes by 31–34%. This variation has no clinical significance. Antibodies to natalizumab circulating in the body increase its clearance by about three times, which corresponds to the observed decrease in the level of natalizumab in patients with circulating antibodies.

The pharmacokinetics of natalizumab in pediatric patients with MS or in patients with hepatic / renal impairment have not been studied.

The efficacy of plasmapheresis in lowering blood levels of natalizumab was evaluated in studies involving 12 patients with MS. The elimination of the drug after 3 plasmapheresis procedures (with an interval of more than 5–8 days) was estimated at 70–80%, which is comparable to 40% found in the previous study for the same period of time after drug withdrawal.

Evaluation of the effect of plasmapheresis on the restoration of lymphocyte migration and, ultimately, on its clinical use has not been carried out.

Indications for use

Tysabri is indicated for use in the following groups of adult patients as a drug capable of modifying the course of multiple sclerosis, as a means of monotherapy for highly active forms of RMS (remitting multiple sclerosis):

a group of patients who cannot be treated with a full and adequate course, for at least one year and at least one drug that changes the course of multiple sclerosis (interferon β): patients should have at least one relapse in the previous year of treatment and at least nine T2 - hyperintense lesions on MRI (magnetic resonance imaging) of the brain, or at least one lesion visible when using contrast agents for MRI, including gadolinium. Patients who do not respond to treatment are considered patients with a constant or increased frequency of exacerbations compared to the previous year, or with ongoing severe exacerbations, despite therapy lasting less than a year;
a group of patients with rapidly progressing severe remitting multiple sclerosis: patients who have had two or more disabling exacerbations during the year and have one or more lesion according to the MRI of the brain, accumulating contrast agents for MRI, including gadolinium, or a significant increase in the lesion volume in the T2 mode compared with the results of the previous MRI.

Contraindications

PML (progressive multifocal leukoencephalopathy);
an increased risk of infection with opportunistic microorganisms, including immunodeficiency states (for example, with current or past therapy with immunosuppressants such as mitoxantrone, cyclophosphamide);
simultaneous use with interferon β or glatiramer acetate;
malignant tumors other than basal cell skin cancer;
children and adolescence;
lactation period (breastfeeding, if necessary, the use of TYSABRI must be discontinued);
increased individual sensitivity to natalizumab or any of the auxiliary components of the drug.

Tysabri, instructions for use: method and dosage

Treatment with TYSABRI should be carried out under the constant supervision of doctors specializing in the diagnosis and treatment of neurological diseases, in specially designated facilities with the possibility of MRI.

Patients receiving TYSABRI should be informed about the risks of this drug and issue a special patient card. After two years of treatment, they should be re-notified of the risks of using TYSABRI, especially the increased likelihood of PML. Caregivers should also be aware of the early signs and symptoms of PML.

Medical institutions should have all the necessary equipment in case of developing hypersensitivity reactions, as well as for conducting MRI.

After preparation of the solution, it is administered in the form of infusion for about 1 hour. During the infusion and within 1 hour after it, patients must remain under medical supervision due to the possibility of allergic reactions.

Tysabri should not be given as an IV bolus.

In the absence of disorders associated with therapy, such as neutropenia, patients treated with interferon β or glatiramer acetate, patients can be transferred directly to natalizumab. When registering violations, treatment with natalizumab begins only after the normalization of indicators.

In patients who have previously received immunosuppressants (azathioprine, mitoxantrone, cyclophosphamide), immunodeficiency should be excluded, since these drugs can cause a long-term immunosuppressive state, which is observed even after their withdrawal.

In the absence of signs of improvement after 6 months of therapy, the advisability of continuing it should be carefully evaluated.

Information on the safety and efficacy of TYSABRI for 2 years was obtained from the results of controlled double-blind studies. If it is necessary to extend the course for more than 2 years, it is required to assess the ratio of possible risk and benefit.

Recommended dosing regimen for adult patients: once every 4 weeks, 300 mg of a solution prepared from a concentrate, in the form of an intravenous infusion.

With repeated administration, the efficacy and safety of TYSABRI have not been determined.

Preparation, administration, storage and disposal of the drug:

Before dilution and administration, inspect the drug and make sure that there are no solid impurities. A concentrate containing solids or not meeting the description “colorless, clear or slightly opalescent liquid” should not be used.
Under aseptic conditions, remove the top cap from the vial, pierce the stopper in the center with a syringe needle and take 15 ml of the concentrate to prepare a solution for intravenous administration.
Add 15 ml of concentrate to 100 ml of 0.9% NaCl solution. To mix the contents of the bottle, gently turn it over several times. Do not shake.
Do not mix TYSABRI with other drugs and / or solvents.
Inspect the diluted solution prior to administration for particulate matter / discoloration. A preparation with foreign impurities or discoloration is not suitable for use.
The prepared solution should be used as soon as possible, but not later than 8 hours after dilution, provided that it was stored at a temperature of 2 to 8 ° C and was not frozen. The solution should warm to room temperature before infusion.
The solution prepared from the concentrate is introduced by intravenous infusion for approximately 1 hour at a rate of ~ 2 ml / min.
At the end of the procedure, it is required to flush the system with 0.9% NaCl solution.
Each vial of TYSABRI is for single use only.
Any unused product or waste must be disposed of in accordance with local regulations.

Side effects

Placebo-controlled studies enrolled 1617 MS patients who received natalizumab for 2 years; the placebo group included 1135 volunteers. Adverse reactions leading to early termination of the course were observed in 5.8% of cases with natalizumab therapy compared to 4.8% in the placebo group. Over the two years of research, adverse reactions that were regarded by the attending physician as related to therapy were observed in 43.5% of patients receiving natalizumab and in 39.6% in the placebo group.

According to the results of placebo-controlled studies of the use of natalizumab in recommended doses in patients with MS during drug infusions, the following undesirable effects were recorded with the maximum frequency: dizziness, nausea, urticaria, chills.

The incidence of adverse events in the natalizumab group was 0.5% higher than in the placebo group.

Reactions indicated by preferred terms used in MedDRA (Medical Dictionary for Regulatory Activity) according to systemic organ classes and frequency [frequent (≥ 0.01 and <0.1), infrequent (≥ 0.001 and <0, 01)]:

infections and invasions: often - urinary tract infections, nasopharyngitis;
from the immune system: often - urticaria; infrequently - hypersensitivity;
from the nervous system: often - headache, dizziness; infrequently - PML;
gastrointestinal disorders: often - vomiting, nausea;
musculoskeletal disorders and connective tissue pathologies: often - joint pain;
general disorders and reactions at the injection site: often - chills, fever, fatigue.

Infusion reactions

In a 2-year controlled clinical study in patients with MS, infusion reactions were considered as side effects that appeared during drug administration or within 1 hour after completion of the procedure. They were observed in 23.1% of patients in the group receiving the drug and in 18.7% in the placebo group. The most common side effects in the natalizumab group were dizziness, nausea, hives, and chills.

Allergic reactions

In a 2-year controlled clinical study in patients with MS, the incidence of hypersensitivity reactions reached 4%, including anaphylactic / anaphylactoid reactions, which occurred in less than 1% of patients receiving TYSABRI.

Typically, hypersensitivity reactions occur during the infusion or within 1 hour after it. According to post-registration observation, reports of allergic reactions were recorded, in which, in addition to more typical symptoms (rash, urticaria), at least one of the following clinical manifestations was noted: shortness of breath, arterial hypotension / hypertension, chest discomfort, chest pain, angioedema edema.

Immunogenicity

In a 2-year controlled clinical study in patients with MS, antibodies to natalizumab were detected in 10% of patients. A two-fold positive result - circulating antibodies to natalizumab - were found in ~ 6% of cases. A single positive response was noted in ~ 4% of cases. Circulating antibodies reduce the effectiveness of TYSABRI and increase the frequency of allergic reactions. Other reactions to IV drug administration due to circulating antibodies included nausea, vomiting, chills, and flushing.

In case of suspicion of circulating antibodies after six months of therapy, or with a decrease in the effectiveness of TYSABRI, or with a reaction to an infusion, it is necessary to do another analysis 6 weeks after the first positive result. Given the likelihood of a decrease in the effectiveness or an increase in the frequency of allergic reactions with circulating antibodies, treatment with TYSABRI should be discontinued.

Infections (including PML) and infection with opportunistic microorganisms

In a 2-year controlled clinical study in patients with MS, the infection rate in the natalizumab and placebo groups was approximately 1.5 per patient-year. The nature of the infections was roughly similar in both groups. Cases of diarrhea due to Cryptosporidium have been recorded. In other clinical studies, other opportunistic infections have been observed, including fatal diseases. In most cases, during infections, patients did not need to interrupt TYSABRI therapy, and with proper treatment, the infection process was resolved.

In the group receiving natalizumab, in clinical studies, a slightly higher incidence of herpesvirus infection (herpes zoster, herpes simplex) in patients was noted than in the placebo group. In the process of post-registration follow-up, serious, life-threatening and sometimes fatal cases of meningitis and encephalitis caused by the herpes simplex virus or herpes zoster virus, the so-called herpes zoster virus, were recorded in patients with multiple sclerosis receiving TYSABRI. chickenpox. The duration of the course of therapy before the development of these phenomena ranged from several months to several years. During the post-registration observation of patients receiving TYSABRI, there were rare episodes of acute retinal necrosis, in some of which herpetic infections of the central nervous system (herpetic meningitis and encephalitis) were recorded. In a small number of patients, severe acute retinal necrosis with concomitant damage to one or both eyes resulted in blindness. In such cases, antiviral therapy was performed, sometimes surgical intervention was required.

During clinical trials, post-registration observational studies and post-registration passive observation, cases of PML have been reported, usually leading to serious disability or death. In addition, as a result of the post-registration use of TYSABRI, cases of JC-viral granular cell neuronopathy, which are similar in symptoms to PML, have been reported.

Liver reactions

During post-marketing surveillance, there have been spontaneous reports of episodes of severe hepatic dysfunction, increased liver enzyme activity and increased bilirubin concentration.

Anemia (including hemolytic)

In the course of post-registration observations of patients receiving therapy with TYSABRI, rare cases of serious manifestations of anemia (including hemolytic) were noted.

Malignant tumors

For more than 2 years of therapy, there was no significant difference in the incidence of malignant neoplasms in patients using natalizumab and in the placebo group. At the same time, longer studies are required to reasonably exclude the effect of natalizumab on the incidence of malignant tumors.

Change in laboratory parameters

In a 2-year controlled clinical study involving patients with MS, treatment with TYSABRI was accompanied by an increase in the level of lymphocytes, monocytes, basophils, eosinophils, as well as nuclear forms of red blood cells in the circulating blood. An increase in the concentration of neutrophils was not observed. The increase in the level of lymphocytes, monocytes, eosinophils and basophils varied from 35 to 140% compared with the initial readings, but the total number of cells remained within normal limits. With TYSABRI therapy, there was a slight decrease in the level of hemoglobin (on average by 0.6 g / dl), hematocrit (on average by 2%) and erythrocytes (on average by 0.1 × 10 ⁶/ l). Usually, these changes were not accompanied by clinical symptoms, and within 16 weeks after the last dose of TYSABRI, all hematological characteristics returned to baseline values. According to post-registration observation, episodes of asymptomatic eosinophilia with an increase in the number of eosinophils exceeding 1500 / mm ³ were also noted. After discontinuation of therapy, these phenomena resolved on their own.

Overdose

No cases of natalizumab overdose have been reported.

special instructions

The physician is obliged to discuss with the patient the benefits and risks of TYSABRI therapy and give him a special card containing basic safety information. It is necessary to instruct patients that with the development of any infection, it is important to warn a medical specialist about the use of TYSABRI.

The physician should inform the patient of the importance of continuous therapy, especially in the first months of using the drug.

Patients on a diet that limits sodium intake should take into account that the sodium content in 1 vial of Tysabri is 2.3 mmol (52 mg).

After dilution of the concentrate in 100 ml of 0.9% NaCl solution, the ready-to-use product contains 17.7 mmol (406 mg) of sodium per dose.

PML (progressive multifocal leukoencephalopathy)

As a result of the use of natalizumab, the risk of developing PML may increase, which may result in death or severe disability.

The likelihood of PML formation increases as the duration of therapy increases, especially when the drug is used for more than 2 years. Information about patients receiving TYSABRI for more than 3 years is currently limited, and therefore it is impossible to assess the risk of their PML at the present time.

In patients who received treatment with immunosuppressants prior to therapy with natalizumab, the risk of PML increases, regardless of the duration of TYSABRI use.

Given the increased likelihood of developing PML, both the doctor and the patient need to individually assess the benefit / risk ratio of treatment. Before starting to work with the drug, the doctor must undergo special training according to the program "Use of the drug Tysabri and observation of patients undergoing treatment."

After 2 years, patients should be re-educated about the risks of using TYSABRI, especially the increased risk of PML. It is important to inform not only patients but also their carers about the early signs and symptoms of this disease.

You can start using TYSABRI only if there is MRI data, which was performed no earlier than three months before the start of treatment. This MRI is basic.

Regular monitoring of the patient's condition is required throughout the entire therapeutic course in order to timely identify emerging new neurological symptoms inherent in PML, or worsening of existing ones.

The emergence of new neurological symptoms requires suspension of therapy until the diagnosis of PML is ruled out.

In order to identify possible symptoms of neurological dysfunction, and if any, determine how typical they are for MS and whether they are a reason for suspicion of PML, the attending physician must continue to monitor the patient. In any doubtful cases, further diagnosis is required, including MRI, the results of which must be compared with the results of the baseline MRI obtained before starting treatment with natalizumab. Also, CSF (cerebrospinal fluid) should be examined for the presence of JC virus (human polyomavirus 2) DNA and repeated neurological examination. If the diagnosis of PML is not confirmed, therapy can be resumed.

The treating physician should be especially alert to symptoms of PML that the patient may not be aware of (for example, signs of cognitive / psychiatric impairment). The patient should be advised to warn close relatives or caregivers that he is undergoing therapy; they will probably be able to see symptoms that the patient did not notice.

The development of PML requires a complete cessation of TYSABRI therapy.

In PML associated with immunosuppression, improvement in clinical outcomes is observed after immunosuppression.

PML and IRIS (immune reconstitution inflammatory syndrome)

Almost all patients who used TYSABRI with the development of PML and subsequent withdrawal of natalizumab had IRIS. Plasmapheresis is used to accelerate the decline in natalizumab levels when PML is diagnosed.

IRIS is the result of the restoration of immunity in patients with PML, which can lead to severe neurological complications, up to and including death.

Careful monitoring of the IRIS syndrome, which usually develops within a few days or weeks after plasmapheresis, in PML patients who received TYSABRI, and appropriate anti-inflammatory therapy when recovering from PML is required.

Infection with other opportunistic microorganisms (including opportunistic ones)

Infection with other opportunistic microorganisms has been described during the use of TYSABRI, mainly in Crohn's disease, other immunodeficiency conditions and concomitant diseases. But such infections can develop in the absence of concomitant diseases. Opportunistic microflora infections have also been observed in MS patients who received natalizumab monotherapy.

When prescribing TYSABRI, one should remember about the likely development of infection with opportunistic microorganisms, which should be included in the list of differential diagnoses. In case of suspicion of infection with opportunistic microorganisms, the course of therapy is suspended until the infection is excluded according to the results of relevant studies.

The development of infection with opportunistic microorganisms requires a complete cessation of TYSABRI therapy.

Allergic reactions

Tysabri is capable of causing hypersensitivity reactions, including serious systemic reactions, which usually develop during solution administration or within an hour after infusion. The risk of hypersensitivity is higher at the beginning of the infusion and with repeated administration of TYSABRI after a long break (from three months or more) following a short course of one or two infusions. However, the risk of developing allergic reactions must be considered with any infusion.

Patients are observed during the procedure and within an hour after the end of the infusion. The medical institution should be equipped with everything necessary for the treatment of hypersensitivity reactions.

The first signs of hypersensitivity reactions require the termination of the administration of the solution and the immediate start of treatment.

Patients who have developed hypersensitivity reactions, TYSABRI therapy should be stopped immediately.

Concomitant or previous treatment with immunosuppressants

The safety and efficacy of using natalizumab in combination with other immunosuppressants or anticancer agents has not been sufficiently established to date. The concomitant use of such drugs can increase the risk of infection, including opportunistic microorganisms, so this combination should be avoided.

Patients treated with immunosuppressants are at increased risk of developing PML. The appointment of TYSABRI to patients who have previously received immunosuppressive therapy requires caution; it is recommended to wait for the resumption of immune system function. Prior to prescribing TYSABRI, the attending physician must evaluate each individual episode to detect possible signs of immunodeficiency.

During the 3rd phase of clinical trials conducted with the participation of patients with MS, it was found that concomitant therapy of recurrence with a short-term course of glucocorticosteroids was not accompanied by an increase in the incidence of infections. Therefore, glucocorticosteroids can be taken for a short time in parallel with TYSABRI therapy.

Immunogenicity

Worsening of the symptoms of the disease or the development of undesirable reactions to the administration of Tysabri may indicate the synthesis of antibodies to natalizumab. In this case, you should test for antibodies to natalizumab twice, with an interval of 6 weeks. With a repeated positive result, therapy is stopped, since the constant presence of antibodies reduces the effectiveness of TYSABRI and increases the likelihood of developing hypersensitivity reactions.

A long break in treatment after a short course of TYSABRI therapy also contributes to an increased risk of developing hypersensitivity reactions with repeated administration of the drug, which requires antibody tests. If the confirmatory test remains positive after 6 weeks, therapy should not be resumed.

Liver reactions

During post-marketing observations, serious spontaneous adverse reactions from the liver were recorded. Hepatic impairment is possible at any time during the course of treatment, even after the first dose of natalizumab is administered. In some cases, when TYSABRI therapy was resumed, the reaction occurred again.

In some patients with a history of liver disease, there was a deterioration in hepatic parameters with TYSABRI therapy. Careful monitoring of the patient's condition is required to identify possible violations of hepatic function. Patients should be warned about the need to contact a medical facility if any symptoms of liver damage, such as jaundice or vomiting, appear.

Significant liver damage requires discontinuation of TYSABRI therapy.

Cancellation of the drug

When the attending physician decides to discontinue therapy with natalizumab, he needs to remember that the drug is present in the circulating blood and continues to exhibit pharmacodynamic effects (for example, leading to lymphocytosis) for approximately 12 weeks after the last infusion. Other drugs prescribed during this period may exhibit drug interactions with natalizumab. The simultaneous use of interferon β and glatiramer acetate, according to clinical studies, poses a threat to patient safety. There is no confirmed information on the safety of administration of TYSABRI to MS patients concurrently with immunosuppressive drugs. The use of these drugs shortly after the end of therapy with natalizumab can induce additional immunosuppressive effects,which is important to carefully consider in each individual case. According to clinical observations, glucocorticosteroids taken short-term for the treatment of recurrent MS do not increase the risk of infection.

After the completion of the TYSABRI course, a certain period of time is required for natalizumab to be flushed out of the systemic circulation.

Influence on the ability to drive vehicles and complex mechanisms

The effect of TYSABRI on the patient's ability to drive vehicles and engage in other potentially hazardous activities has not been studied. Based on the mechanism of action of natalizumab, the likelihood of drug exposure to these abilities is low. However, during therapy, cases of dizziness are often noted, and patients with such an undesirable reaction should refrain from performing types of work that require increased concentration of attention and speed of psychomotor reactions.

Application during pregnancy and lactation

Data on the use of natalizumab during pregnancy are limited. Reproductive toxicity has been identified in animal studies. The possible risk to humans is unknown. TYSABRI should not be prescribed unless absolutely necessary during pregnancy. In case of pregnancy while using TYSABRI, treatment should be discontinued.

Natalizumab is excreted in breast milk during lactation; its effect on newborns or infants is unknown. In this regard, the use of TYSABRI requires the termination of breastfeeding.

Pediatric use

Tysabri is not used in pediatrics.

With impaired renal function

Studies of the effectiveness of TYSABRI in patients with impaired renal function have not been conducted.

The mechanism of excretion and the results of studying the pharmacokinetic characteristics suggest that TYSABRI can be administered to patients with impaired renal function without dose adjustment.

For violations of liver function

Studies of the effectiveness of TYSABRI in patients with impaired liver function have not been conducted.

The mechanism of excretion and the results of studying the pharmacokinetic characteristics suggest that TYSABRI can be administered to patients with impaired hepatic function without dose adjustment.

Use in the elderly

It is not recommended to prescribe TYSABRI to patients over 65 years of age due to the lack of data on its safety for this age category.

Drug interactions

The safety / efficacy of natalizumab in combination with other immunosuppressants or anticancer drugs is currently insufficiently established. The concomitant use of these drugs can increase the risk of infection, including infection with opportunistic microorganisms, so this combination of drugs is contraindicated.

Patients who have previously received immunosuppressive therapy are at increased risk of PML and should be used with caution when prescribing natalizumab. It is recommended to wait until the immune system is restored. When prescribing TYSABRI, the attending physician must assess the patient's condition in each individual case in order to identify potential signs of immunodeficiency.

Concomitant treatment of recurrent MS with a short course of glucocorticosteroids was not accompanied by an increased incidence of infections. It is possible to carry out short-term therapy with glucocorticosteroids in parallel with the use of TYSABRI.

Tysabri is contraindicated in combination with other drugs that alter the course of multiple sclerosis.

Tysabri concentrate should not be mixed with any other medicinal products or solutions, except for 0.9% NaCl solution.

In open randomized studies in patients with multiple sclerosis, no significant abnormalities in the immune response to the administered antigen were found. The comparison was carried out in the group of patients treated with Tysabri for 6 months, and in the control group, who received placebo.

Analogs

Tizabri analogs are Lemtrada, Campas, etc.

Terms and conditions of storage

Keep out of the reach of children.

Store the concentrate and solution, ready for use, at a temperature of 2 to 8 ° C, in a place protected from light. Do not freeze.

The ready-to-use solution is stored for no more than 8 hours.

The concentrate has a shelf life of 4 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about TYSABRI

Natalizumab is a relatively new second-line drug for MS, therefore patient reviews of TYSABRI are currently insufficient to obtain a reliable picture of the drug's effectiveness.

Since multiple sclerosis is a serious disease with significant clinical and social consequences, there is always a special need to find new drugs for more effective treatment. Experts say that the high efficacy of natalizumab provides a decrease in indicators of disease activity such as the clinical relapse rate and the rate of disease progression on the EDSS scale, significantly improves the health-related quality of life, as well as the physical and cognitive functions of patients. It was found that the use of natalizumab leads to a persistent decrease in disability and the absence of disease activity.

Due to the fact that the benefits of natalizumab are balanced with the risks of its use (the development of PML and other opportunistic infections is possible), the ability of both doctors and patients to monitor the symptoms of the disease is very important for the early diagnosis of PML, since the timely discontinuation of natalizumab if PML is suspected can significantly improve the observed outcomes.

The price of TYSABRI in pharmacies

The approximate price of TYSABRI, a concentrate for the preparation of a solution for infusion, 20 mg / ml, 15 ml in a bottle (bottle) varies from 103,500 to 121,696 rubles per bottle.

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!